Long chain glycolipids useful to avoid perishing or microbial contamination of materials

ABSTRACT

The invention relates to the use of, and methods of use employing, certain glycolipid compounds as defined in detail below and having preservative or antimicrobial properties, novel compounds of the glycolipid class, and related invention embodiments. 
     The compounds have the formula I 
     
       
         
         
             
             
         
       
     
     wherein m is 3 to 5, n is 2 to 5, o is 0 or 1 and p is 3 to 17, with the proviso that the sum m+n+o+p is not less than 14; and
 
R is a carbohydrate moiety bound via one of its carbon atoms to the binding oxygen,
 
and/or a physiologically, especially pharmaceutically or nutraceutically or cosmetically, acceptable salt thereof, or an ester thereof,
 
as such or in the form of a composition,
 
where the compound may be present in open chain form and/or in the form of a lactone (FIG.  1 ).

SUMMARY OF THE INVENTION

The invention relates to the use of, and methods of use employing,certain glycolipid compounds as defined in detail below and havingpreservative or antimicrobial properties, novel compounds of theglycolipid class, and related invention embodiments.

These and related invention embodiments are described below and in theclaims which are incorporated into the specification by reference.

BACKGROUND OF THE INVENTION

Bacteria and other microbial organisms cause food and beverage products,cosmetic and home care products as well as other products to go bad,thereby reducing the shelf life or useful life of such products orgoods. Thus, numerous efforts have been made to reduce the deleteriouseffects of microbial contaminants in food and beverage products,cosmetics, dressing material and other materials, e.g. medical devicessuch as implants.

Other food preservatives such as salt, sugar and vinegar have been usedfor generations and while relatively safe to use, their preservativeeffect is limited in both duration of effect and the types of food andbeverages for which they can be used. In addition, at higher levels,preservatives such as salt and vinegar can affect the taste of theproduct.

Commonly used preservatives for cosmetics include antimicrobial agentssuch as quaternary ammonium compounds, alcohols, chlorinated phenols,parabens and paraben salts, imidazolidinyl urea, phenoxyethanol,p-hydroxybenzoate, small carboxylic acids like benzoic acid, sorbicacid, salicylic acid, formic acid, proponic acid or corresponding salts.Formaldehyde-releasers and isothiazolinones may also be used.

However, these materials often may not be tolerated or, e.g. in the caseof formaldehyde, may even be toxic and even carcinogenic, or they maycause allergies or food intolerance.

Another preservative e.g. used in food and especially beverages issulfuric acid, while in meat products, e.g. sausages, preserved meat andmeat, stabilizers which decrease water activity such as potassium and/orsodium nitrites and nitrates are often added. Also smoke is often usedfor preserving meat products, with the undesirable side effect offormation of polycyclic aromatic hydrocarbons which have carcinogenicproperties.

Food and beverages have varying degrees of sensitivity tomicrobiological spoilage depending on intrinsic factors of the food orbeverage such as pH, nutrient content (e.g., juice, vitamin, ormicronutrient content), carbonation level, Brix (an indicator of sugarcontent), water quality (e.g., alkalinity and/or hardness), andpreservatives.

Spoilage events occur when microorganisms are able to overcome theproduct's intrinsic protection factors and grow. The microorganisms'ability to overcome these hurdles can be influenced by, among otherthings, initial contamination level, temperature, water content, e.g.water activity, and package integrity. Of special importance are alsorecurrent contaminations of cosmetics, e.g. by hand contact duringnormal use.

A number of organisms are responsible for spoiling a variety ofbeverages materials, including cold-filled beverages. Yeasts such asSaccharomyces, Zygosaccharomyces, Candida, and Dekkera spp. are mostcommon. Also, acidophilic bacteria such as Lactobacillus, Leuconostoc,Gluconobacter, and Zymomonas spp., and molds like Penicillium,Aspergillus and Mucor spp. can spoil various water containing materials.

Other materials and also other types of beverages are susceptible tospoilage by microorganisms. Spores of acidophilic, thermophilicbacteria, such as Alicyclobacillus spp., and heat resistant mold sporesof Byssochlamys, its anamorphic (asexual) stages Paecilomyces, andNeosartorya spp. can survive pasteurization and may spoilnon-carbonated, hot-filled products such as sport drinks and teas. Also,packaged waters are susceptible to contamination by molds.

In cosmetic, personal care and home care products spoilage occurs by avariety of micro-organisms, ranging from Gram-positive bacteria (e.g.Staphylococcus spp.), Gram-negative bacteria (e.g. Escherichia coli,Pseudomonas spp.) to yeasts (e.g. Candida albicans) and common molds(e.g. Aspergillus niger). Microbial growth in or on these productsdepends on several instrinsic factors such as water activity of theformulation (minimum water activity requirements for growth orproliferation range from 0.99 for Acinetobacter species down to 0.61 forsome fungal species), formulation composition, pH value (e.g., optimumpH for the growth of most yeasts and molds is between 4.0 and 6.0), andprocessing conditions such as temperature. While high temperatures, e.g.80° C. for 20 minutes, may reduce microbial contaminations duringprocessing, it is important to prevent inactivation or degradation ofthe preservatives in the formulation. Furthermore, product packaging,solubility of the preservative and its antimicrobial susceptibilityprofile will influence preserving efficacy and, consequently, the shelflife of the products.

Protection against microbiological spoilage of sensitive products can beachieved using chemical preservatives and/or processing techniques suchas hot filling, tunnel pasteurization, ultra-high temperature (UHT), orpasteurization followed by aseptic packaging, and/or pasteurizationfollowed by chilling the beverage. Generally, beverages with a pH<4.6can be chemically preserved, heat processed, and filled into packagessuch that the product is not re-contaminated. For example, processtechniques such as cold-filling, followed by chemical preservatives orpasteurization with cold filling, may be used to preserve a cold-filledbeverage. In a similar manner, this same beverage may be processed usingnon-preserved techniques such as hot filling, tunnel pasteurization,pasteurization followed by aseptic filling, or requiring the beverage tobe chilled, i.e., under refrigeration following the pasteurization step.Beverages having a pH 2-4.6 must be processed such that spores aredestroyed using ultra-high temperatures followed by aseptic filling intopackages or by using a retort.

Current preservation systems for acidic, shelf-stable, carbonated andnon-carbonated food or beverages, e.g. soft drinks, generally rely onweak acid preservatives (e.g., benzoic and/or sorbic acid). Benzoic andsorbic acids (and salts thereof) effectively inhibit yeasts, bacteria,and molds with some exceptions. Weak acids in beverages exist inequilibrium between their dissociated and undissociated forms, which isdependent upon the dissociation constant of the acid (pKa) and thebeverage's pH. The pKa for benzoic acid is 4.19 and the pKa of sorbicacid is 4.76. A beverage pH below the pKa of the involved acid pushesthe equilibrium towards the undissociated form. The undissociated formis more efficacious against microorganisms; therefore, weak acidpreservatives are most effective in the low pH range.

The preservation properties of weak acids may be enhanced by theaddition of preservative enhancers, such as chelating compounds, to thematerial to be preserved, e.g. a food, beverage or cosmetic preparation.For example, common chelating compounds added include calcium disodiumethylenediaminetetraacetic acid (EDTA) or one or more of thepolyphosphates such as sodium hexametaphosphate (SHMP).

In high nutrient, non-carbonated products, such as those beveragescontaining juice, vitamins, and/or minerals, the weak acids are morelikely to exert inhibition if used in conjunction with preservativeenhancers. Also weak acid preservation systems, however, havelimitations:

Genetic adaptation and subsequent resistance by microorganisms is one ofthe biggest concerns (see Piper. et al., Microbiol. (2001) 147:2635-2642). Certain yeasts such as Z. bailii, Z. bisporus, Candidakrusei, and S. cerevisiae have specific genes that enable them to resistthe weak acid preservatives and grow. This happens despite the presenceof preservatives and regardless of the co-presence of EDTA or SHMP. Somebacteria such as Gluconobacter spp. are also thought to be preservativeresistant. The levels of weak acids necessary to overcome thisresistance have been shown to be far beyond regulatory limits on uselevels. Most often, spoilage of preserved teas, juice-containingbeverages, and carbonated beverages is due to preservative resistantmicro-organisms.

Medium chain saturated fatty acids and their esters witholigohydroxylated compounds have been found to possess inhibitoryeffects against several bacteria and fungi. The minimum inhibitoryconcentration values reach a maximum with a chain length of about 8 to12 carbon atoms (Varvaresou, Int. J. Cosmetic Sci (2009) 31: 163-75).

In addition, the other process techniques for low acid beverages (i.e.,pH 4.6) have limitations. Such low acid beverages should bethermally-treated sufficiently to destroy spores of Clostridiumbotulinum and Bacillus species (B. cereus, B. subtilis and others).Examples of such processes include UHT and retort. Even after suchprocessing, the beverage products should be handled in a way to preventpost-processing contamination. Research, however, suggests that theremay still be various strains of microorganisms that can survive thosedifferent processing techniques. To that end, those processingtechniques may not eliminate the potential for spoilage.

Other chemical preservatives can likewise cause adverse side effectswhen consumed. Thus, many existing preservatives must be regulated andhave legally imposed upper limits on usage. In addition, manypreservatives, such as sodium benzoate, proprionates, aromatic benzenes,organic acids, propylene glycol and glycerol, for example, when used atlevels sufficient for antimicrobial effects, impart an unpleasant tasteon the beverage or food, masking or altering to some degree the tasteexpected by the consumer. Weak acids can impart throat or mouth burnwhen used at high levels. Although there are certain shelf-stablebeverages where this attribute may be acceptable, this sensoryperception is often considered negative. Similarly, polyphosphates usedin weak acid preservation systems can have some limitations. Forexample, polyphosphates can impart off-flavors to a beverage.

Certain emollient solvents exhibit synergistic action when combined withessential oils or ingredients against microorganisms as noted in WO03/034994, which is incorporated by reference in its entirety. Theemollient solvents used as preservatives in cosmetics do not usuallyproduce skin reactions, and in addition, render the skin smooth andsilky.

In a series of publications Nishida et al. reported on compounds of anunidentified strain of “Basidiomycetes sp.” to produce glycolipids whichare assumed to exhibit inhibitory activity against Gram-positivebacteria (Nishida, Tetrahedron Lett 1988, 29(41): 5287-90; Chem PharmBull 1990, 38(9): 2381-9; J Antibiot 1991, 44(5): 541-5; Chem Pharm Bull1991, 39(11): 3044-7; Proc “Symposium on the chemistry of naturalorganic compounds” 1987, 29: 729-36; ibid 1990, 32: 253-9) and againstinfection by polio and herpes virus (J Chrom 1994, 664(2): 195-202; JMass Spectrom Soc Jpn 1995, 43(1): 27-36; ibid 37-44). Much effort wasdone in the structure elucidation and the results were presented indetail in the above cited publications; nevertheless the authors did notpresent any data of the suggested antimicrobial activity. Later on, oneof the compounds isolated by Nishida et al. (Glykenin IVA) was reportedas antifungal agent from a Dacrymyces sp. (Wunder, A., Diss. 1995, Univ.Kaiserslautern, Germany). Mierau (Z Naturforsch 2003; 58c: 541-6) madereference to this work. In neither of the cited publications, details onthe biological data and the identity of the producer organisms werereported.

JP 2006-176438 A and J. Antibiot. 2007, 60, 633-639 disclose F-19848 A,a glyocolipid obtained from the fermentation broth of the fungus strainDacrymyces sp. SANK 20204, as inhibitor of hyaluronic acid bindingreceptor CD44 and as being useful for treating or preventingdegenerative arthritis or a disease caused by the degenerativearthritis.

Biosurfactants are produced extracellularly or as a part of the cellularmembrane by various organisms such as bacteria and fungi. Theirstructures usually contain a hydrophobic non-polar moiety that consistsof unsaturated, saturated, and/or oxidized lipids or fatty acids, and ahydrophilic component, which may be composed of amino acids,carbohydrates, phosphates or cyclic peptides. They are generallyclassified into glycolipids, lipopeptides, phospholipids, fatty acidsand polymeric compounds according to their chemical structures.Biosurfactants are produced by a wide range of microorganisms andtherefore differ in their chemical structure. Some biosurfactants haveantimicrobial activity against bacteria, yeasts, molds or viruses.Moreover, they can prevent microbial colonization of surfaces such asthose of implanted medical devices through their ability to disrurptbiofilms on these surfaces.

Sophorolipids, rhamnolipids and mannosyl-erythritol lipids are the mostwidely used glycolipid biosurfactants in cosmetics.

Rhamnolipids are known for their efficiency in remove of nosocomialmicrobes in biofilms. A biofilm is characterized by a strong adherenceactivity of the engaged microorganisms. Known biosurfactants withanti-adhesive or biofilm disrupting activity are produced byLactobacillus acidophilus, L. fermentum, Lactococcus lactis,Streptococcus thermophilus, Bacillus subtilis, B. licheniformis,Brevibacterium aureum, Pseudomonas aeruginosa, and P. putida.

The genus Lactobacillus produces the lipopeptide surlactin, the genusBacillus produces lipopeptides belonging to the fengycin-like andsurfactin-like families of secondary metabolites. Another lipopeptidehas been isolated from Brevibacterium aureum. Streptococcus thermophilusis a producer of yet unidentified glycolipids, which contain sizeableamounts of nitrogen (Rodrigues, Colloids & Surfaces B: Biointerfaces(2006) 53: 105-112). Further known producers of biosurfactantsexhibiting activity against microorganisms involved in biofilms arePseudomonas aeruginosa which produces rhamnolipids, and P. putida, whichproduces lipopeptides. The nitrogen containing biosurfactants producedby Streptococcus mitis were not yet identified. Lactococcus lactisproduces a low molecular weight [467 Da] biosurfactant consisting ofmethyl-2-O-methyl-beta-d-xylopyranoside with octadecanoic acid.(Saravanakumari & Mani, Bioresour Technol (2010) 101:8851-8854).

A good overview of different classes of known biosurfactants is given byRahman et al. (Biotechnology (2008): 360-70) presenting great advantagesof theses compounds against synthetic compounds such as a lowertoxicity, higher biodegradability, a better environmental compatibilityand their ability to tolerate extreme temperature, pH and salinity.Nevertheless the reported difficulties in the production teach thelimitation of industrial usage as being relative low yields, highfermentation costs and difficult isolation procedures within industrialprocesses. Acceptable economic production of biosurfactants in largescale is suggested by the use of industrial wastes as process media.

As commonly understood in the art, the definitions of the terms“preserve”, “preservative,” and “preservation” do not provide a standardtime period for how long the matter to be preserved is kept fromspoilage, decomposition, or discoloration. The time period for“preservation” can vary greatly, depending on the subject matter.Without a stated time period, it can be difficult or impossible to inferthe time period required for a composition to act as a “preservative”.

In summary, many preservatives and preservation methods have undesirableside effects, such as toxicity, allergenicity, carcinogenicity,occasionally formation of resistance, and/or often are not accepted bythe consumers in a time where natural preservation is preferred overpreservation with synthetic or other products having a negative healthimage.

Accordingly, a great need exists for effective, relatively inexpensive,non-toxic, naturally derived preservative compositions that avoiddisadvantages as mentioned and are capable of reducing microbialcontamination and concomitant spoilage in a wide range of perishablefood, beverages, cosmetics, and other consumer goods, but withoutappreciably altering the taste, color, odor, or function of the product.

GENERAL DESCRIPTION OF THE INVENTION

Surprisingly, new compounds were found and isolated from strains ofDacryopinax spathularia and other fungal strains belonging to theDacrymycetaceae family, and for them as well as for compounds of thesame class it has been found that they have novel and useful properties.The compounds are described in more detail below.

The class of compounds of the formula I, both insofar as they are notnovel as well as they are novel, is not known in the art for anyspoilage/perishing preventing activity.

Very surprisingly therefore, it has been found that these compoundsexhibit a strong inhibition activity against microorganisms which areresponsible for spoiling or deterioration of orally consumable products(such as food products and beverages) or cosmetic compositions. Forexample, an extract of Dacryopinax according to the present inventioncan show a broader activity spectrum than the corresponding singlecomponents of the produced glycolipid complex (glycolipid mixture) thathave been isolated to purity. Such multi-component mixtures exhibit aremarkable long term activity against numerous important spoilagemicrobes, including e.g. Zygosaccharomyces and Bacillus species.

Further surprisingly, the microorganisms used in the present inventionallow producing large amounts of the compounds of formula I in a costeffective production process.

They are, for example, able to reduce growth of microbial contaminantssuch as bacteria, yeasts, molds and other microorganisms and theirspores, especially those which are temperature resistant e.g.thermophilic or heat resistant, or acidophilic e.g. microorganisms whichtolerate a lower pH value that cause spoilage of food, beverages,cosmetics and other materials.

The glycolipids do not exhibit a distinctive taste or unpleasant mouthfeeling and therefore this application relates to the use of glycolipidsin materials which get in contact with the oral cavity of a human. Thisapplication also relates to synergistic combinations of antimicrobialingredients that can be used in orally consumable compositions, such asfood and beverages, without imparting off-flavors.

Yet surprisingly it was found that the use of a simple medium only usingdextrose or glucose as carbon source and a small amount of yeast extractcan be superior against typical complex media known from the literature.However, also the use of other media or growth substrates is included.Furthermore it was found that this culture medium supported particularlyhigh production rates at relatively low biomass production, whichfacilitated downstream processing of the crude glycolipid products,allowing their easy recovery from the culture fluid by precipitation.

The glycolipids of the present invention can be shown to demonstrate abroad antimicrobial spectrum and can be incorporated as additives intovarious materials as a preservative or an agent with preservingactivity, especially as cosmetic additive and/or food additive and/orbeverage additive based on this antimicrobial activity.

Although the mechanism of action for the glycolipids is unknown, thesecompounds can, without that this is intended to mean a comprehensive andconcluding definition of their properties, be considered asbiosurfactants and, additionally, might influence the cell membranes ofmicroorganisms. Other known biosurfactants are rhamnolipids,sophorolipids, lipopeptides like chlamydocin, surfactin, lichenysin G,etc. as cited by Mukherjee (in “Biosurfactins”, R Sen ed., Springer,2010, chapter 4, “Microbial Surfactants and Their PotentialApplications”). The cited biosurfactants differ from the compounds offormula I of the present invention. Although Mukherjee listed compoundsnamed as glycolipids, the structures of these compounds differsignificantly from those of the present invention:

The compounds useful according to the invention are in generalcharacterized

by a long chain fatty acid with at least 20 carbon atoms;by a carbohydrate moiety which is not attached to the acid group:by an alpha hydroxyl group;and by at least one further hydroxyl group, in the “center” of the fattyacid carbon chain, clearly separated from both the alpha position andthe glycosyl substituent.

Especially compounds of the formula I represented below which areesterified in their carbohydrate moiety by other acids than acetic acid,in particular esterified by isovaleric acid, are not known in the artand thus novel.

DETAILED DESCRIPTION OF THE INVENTION

In a first embodiment, the invention relates to the use of a compound ofthe formula I, or a mixture of two or more such compounds of the formulaI,

wherein m is 3 to 5, n is 2 to 5, o is 0 or 1 and p is 3 to 17, with theproviso that the sum m+n+o+p is not less than 14; andR is a carbohydrate moiety bound via one of its carbon atoms to thebinding oxygen, and/or a physiologically, especially pharmaceutically ornutraceutically or cosmetically, acceptable salt thereof, or an esterthereof,as such or in the form of a composition,where the compound may be present in open chain form and/or in the formof a lactone,as agent with preservative or antimicrobial properties, comprisingadding the agent to a material, where said material is preferablyselected from the group consisting of a cosmetic, a food, a beverage, apharmaceutical, a medical device, a home care, and an active packagingmaterial.

Preferred is the use, where in the compound of the formula I, m is 3 to5, n is 2 to 5, o is 0 or 1, p is 5 to 15 and R is a moiety of thesubformula

wherein the rings A, B and C are monosaccharide moieties eachindependently from the others with 5 or 6 ring members, wherein one ormore of the hydroxyl groups may be acylated.

In other terms: A compound for use according to the invention isespecially a linear carboxylic acid with at least 20 carbon atoms,preferably 22 to 28, 24 to 26, in particular 26, substituted at position2, that means the alpha position, with a hydroxyl group; substitutedwith a second hydroxyl group at the omega-5, omega-6 or omega-7 positionwhich is itself substituted by a carbohydrate, e.g. as defined below,and one additional (a third) hydroxyl group between the omega and thealpha substituents which is separated from the second one by two to fivemethylene groups, where optionally this third hydroxyl group has avicinal hydroxyl group, in the direction of the acidic end.

In another embodiment of the invention, the compound or compounds of theformula I, a physiologically acceptable salt thereof, and/or an esterthereof, is added in the form of an extract from a natural source orobtained from such an extract. Preferably, the source of the extract isa fungus belonging to family Dacrymycetaceae, a species of the generaDacryopinax, Ditiola, Guepiniopsis and/or Femsjonia, more especiallyDacryopinax spathularia, Dacrymyces sp., Dacrymyces stillatus,Dacrymyces chrysocomus, Guepiniopsis buccina and/or Femsjonia luteo-alba(=Ditiola pezizaeformis). Especially preferred are Dacryopinaxspathularia strain MUCL 53181, Dacryopinax spathularia strain MUCL53182, Ditiola radicata strain MUCL 53180, Ditiola nuda strain MUCL53179, Dacrymyces chrysocomus strain CBS280.84 and Femsjonia luteo-alba(=Ditiola pezizaeformis) strain MUCL 53500.

In our investigations we found Dacryopinax spathularia strain MUCL 53181to be the best strain for identified so far for producing the compoundsof formula I and mixtures of two or more compounds of formula I, inparticular those described in detail hereinafter, particularly thecompounds of formula I exhibiting the strongest antimicrobial activityagainst yeasts and molds. Thus, in a further aspect the presentinvention also relates to Dacryopinax spathularia strain MUCL 53181 assuch.

Another embodiment relates to the use as described above or below of oneor more compounds of the formula I, where the material to which suchcompound(s) are applied is subjected to a heat treatment before, duringor after addition of the compound(s) of the formula I, a physiologicallyacceptable salt thereof and/or an ester thereof.

In another embodiment, the invention relates to a novel compound of theformula I, or a mixture of two or more compounds of the formula Iincluding a novel compound of the formula I, where the compound orcompounds may be present in open chain form and/or in the form of alactone, and/or a pharmaceutically or nutraceutically or cosmeticallyacceptable salt thereof, as such.

Another embodiment of the invention relates to a compound or a mixtureof compounds of the formula I shown above or as defined above or below,where the moiety R carries at least one hydroxyl group esterified withan acid with 3 or more carbon atoms, a physiologically acceptable salt,and/or an ester thereof, especially wherein the acid is aC₃-C₁₀-alkanoic acid, especially isovaleric acid; a physiologicallyacceptable salt, and/or an ester thereof, more especially a compoundselected from the group of compounds represented by the followingformulae:

and/or a physiologically acceptable salt, and/or an ester of the acidgroup thereof.

In yet another embodiment, the present invention relates to apreservative or antimicrobial composition, comprising as active agent acompound or a mixture of compounds of the formula I, a physiologicallyacceptable salt thereof, and/or an ester thereof, as shown or defined inany one of claims 1, 3, 4 and 8 to 15, alone or with another additive,such as a carrier material, where the preservative composition isespecially for use in a cosmetic, a food, a beverage, a pharmaceutical,a medical device, or an active packaging material, especially in theform of a powder or a liquid, e.g. a composition which is a coating orfilm. The composition, in a more specific embodiment of the invention,may be a precursor of a beverage, especially a concentrate, a syrup or apowder.

In another embodiment, the composition defined in the precedingparagraph is an antimicrobial composition for enhancing the stabilityagainst microorganisms, especially where at least one microorganism isselected from the group consisting of mold, yeast and bacteria.

In another embodiment, the composition according to any one of the twopreceding paragraphs is a preservative or antimicrobial composition fora pharmaceutical, a medical device, a food container, a beveragecontainer, or especially a food, a beverage, a cosmetic, or a home careproduct.

In another embodiment, the composition according to any one of the twopreceding paragraphs is a biofilm inhibiting agent and used as such byadministering, or in methods comprising administering, one or morecompounds of the formula I, or a composition comprising it, to surfacesor materials coming into contact with surfaces. This way biofilms onvarious materials including medical devices, teeth, containers, homecare products, pipes or mains or other liquid conducting or containingdevices and the like can be avoided.

In yet another embodiment of the invention, the composition according toany one of the preceding four paragraphs comprises an additionalpreservative.

The invention, in yet another embodiment, also relates to an extractcomprising one or more compounds of the formula I, a physiologicallyacceptable salt thereof, and/or an ester thereof, as shown or definedabove or below.

A further invention embodiment relates to a method of enhancingmicrobial stability of a material, comprising adding to said materialone or more compounds of the formula I, a physiologically acceptablesalt thereof, and/or an ester thereof, as shown or defined above orbelow, preferably a material selected from the group consisting of acosmetic, a food, a beverage, a pharmaceutical, a home care, a medicaldevice, and an active packaging material, especially a beverage, or afood, or a cosmetic.

Another embodiment of the invention relates to a material comprising, asor within a coating and/or as admixture, an additive in the form of acompound or a mixture of compounds of the formula I, a physiologicallyacceptable salt thereof and/or an ester thereof, as defined above orbelow. This material must be other than the fungus from which thecompound or compounds of the formula I are extracted. In anotherembodiment of the invention, the material is a cosmetic, a food, abeverage, a pharmaceutical, a home care, a medical device, or an activepackaging material, especially a beverage, a beverage precursor,especially a concentrate, syrup or powder, a food or a cosmetic. Inanother embodiment, such material comprises an additional preservative.

Another invention embodiment relates to a material according to thepreceding paragraph, which is obtained after heat treatment.

The invention also relates to a method of extracting and/or isolatingone or more compounds of the formula I, especially as described belowand/or in the Examples.

The invention also relates to the embodiments in the claims andespecially the dependent claims which are herewith incorporated byreference into the description.

The compounds of the present invention or useful according to thepresent invention of the formula I, according to present knowledge, areproduced only by fungi of the family Dacrymycetaceae, particularly byfungi of the genera Dacryopinax (e.g. D. spathularia), Dacrymyces,Ditiola (e.g. Ditiola radicata or Ditiola nuda), Guepiniopsis andFemsjonia (e.g. F. luteo-alba). All these fungi have in common that theybelong to family Dacrymycetaceae. All species of Dacrymycetaceaehitherto known are wood-inhabiting saprotrophs, which may either causebrown rot or white rot (Seifert, Mycologia 75 (1983): 1011-1018). Eventhough they can be isolated easily from spores of basidiocarps growingin the field and readily grow in culture, relatively few strains ofDacrymycetes are deposited in public collections.

The fungal genus Dacryopinax G. W. Martin was erected by Martin (Lloydia11 (1948): 111-122) and currently comprises 23 accepted taxa, including22 species and one variety (fide Mycobank; http://www.mycobank.org).According to the latter database, the genus is presently classified inthe Basidiomycota, class Dacrymycetes, order Dacrymycetales, familyDacrymycetaceae. Members of the Dacrymycetes (previously often referredto as order Dacrymycetales before it was elevated to class rank), arecharacterized by their unique basidial morphology with twoequidiametrous epibasidia, thus shaping the basidium like a tuning fork.In addition, they have dolipores with continuous parenthesomes.

These common morphological and ultrastructural features were supportedvery well in various molecular phylogenetic studies, as reflected byHibbett (Mycologia 98, 917-925, 2006) and references cited therein. Mostspecies of the Dacrymycetes still belong to order Dacrymycetales, familyDacrymycetaceae. The latter family comprises eight genera, which havebeen traditionally separated on the basis of macroscopical (primarilyrelating to the basidiocarp habit) and microscopical (e.g., the wallthickness of marginal hyphae in the sterile parts of basidiocarps)morphological characters of the fruiting bodies (i.e., basidiocarps).However, this classification is not unequivocal and therefore gave riseto various alternative taxonomic concepts over the past decades. Forinstance, McNabb (N. Z. J. Bot 3, 59-72, 1965), gave the firstcomprehensive treatment of Dacryopinax and circumscribed its basidiocarphabit as follows; “Fructifications extremely variable in shape,stipitate with a spathulate, petaloid, flabellate, cupulate, obliquelycupulate, inversely cupulate, foliose, or occasionally lobed andsomewhat morchelloid pileus” This circumscription, which is still validuntil today, suggests that Dacryopinax is a complex genus. In addition,recent molecular phylogentic studies by Shirouzu et al (Mycoscience48:388-394, 2007 and Persoonia 23, 16-34, 2009) suggested thatconvergent evolutionary developments in the Dacrymycetales andDacrymycetaceae might have given rise to development of similarmorphological features, hence the basidiocarps that are characteristicof Dacryopinax and other genera of Dacrymycetaceae might have evolvedindependently more than once.

The currently accepted type species of Dacryopinax is Dacryopinaxelegans. However, by far the most cited species in the literature isDacryopinax spathularia (Schwein Fr.) G. W. Martin. This species wasfirst described from South Carolina, USA, and had been treated underdifferent names (i.e., Merulius spathularius, Guepinia spathularia)before Martin proposed the genus Dacryopinax. Under Guepinia spathularia(which is an invalid, later synonym of a plant genus name and thereforehad to be abandoned), this fungus was already reported to occur invarious tropical and subtropical regions of the world, includingNorthern Australia, New Zealand, Asia and America by Saccardo, P. A.,Sylloge Fungorum 6, p 808 (1888) and has since then been reported fromnumerous other countries of the world. Dacryopinax spathularia possessesan unusual geographical distribution. According to McNabb (N.Z.J. Bot 3(1965): 59-72) it is widely distributed throughout both hemispheres, buthas never been found in Europe, though it occurs in North Africa andeastern Russia. The species is characterised by having variable, albeittypically spathulate basidiocarps of up to 2.5 mm height, uniseptatespores, and thick-walled, cylindrical abhymenial hairs.

Dacryopinax spathularia is one of the species in the family and orderwhich is capable of producing comparably large basidiocarps. It wasreported to be used as “edible mushroom” by the indigenous population ofCameroon (Van Dyck et al., Ambio 32 (2003): 19-23). The entire fungalfamily Dacrymycetaceae does not contain any poisonous species, eventhough the basidiocarps of most species are rather inconspicuous and/orhave a tough, rubbery consistence that prevents their culinary use.Interestingly, the cultures of certain Dacrymyces species, which can beregarded as closely related to Dacryopinax, have been patented for theirutility in production of carotene pigments (U.S. Pat. No. 2,974,044).Carotenoids are also apparently the only secondary metabolites that wereso far reported from a species of Dacryopinax, and their production inthe cultures of D. spathularia have been studied in detail by Vail &Lilly (Mycologia 60 (1968): 902-907).

The fungal strains that produce the compounds of the present inventionwere characterised by morphological methodology, using phase contrastmicroscopy of cultures grown on solid YMG medium, and by molecularphylogenetic methods. Since the LSU or 28S/5.8S nuc-rDNA had recentlybeen reported to be informative for the phylogenetic assessments of theDacrymycetes by Shirouzu et al (Persoonia 23, 16-34, 2009), and theauthors of the latter paper published numerous reliable referencesequence data, this region of the DNA was chosen for comparison uponcharacterisation of the strains of Dacrymycetes that are the subject ofthe present invention.

DNA for PCR was isolated from YMG cultures. The 28S/5.8S nuc-rDNAregions were then amplified using primers LR7 and 5.8SR (Vilgalys Lab,Duke University, Durham, USA,http://www.biology.duke.edu/fungi/mycolab/primers.htm), using the PCRTaq PCR Core Kit (Qiagen, Hilden), and applying a standard thermalprofile with an annealing temperature of 53° C. Amplification productswere purified using SigmaSpin Post-Reaction Clean-Up columns(Sigma-Aldrich), using the protocol supplied by the manufacturer.Nucleotide sequences were obtained by cycle sequencing using a DNA CycleSequencing Kit (Jena Bioscience, Jena, Germany) and 5′ IRD700-labelledprimer LROR (Vilgalys Lab). Labelled primers were custom synthesized byEurofins MWG Operon, Ebersberg, Germany). The cycle sequencing productswere then analysed using a LI-COR 4200 (Li-Cor Bioscience, Lincoln, NB)genetic analyser. In the following the characteristics of five strainsthat were identified of producers of the glycolipids that are subject ofthe current invention are briefly summarised.

Strain FU50088 was isolated from the sporocarp of an unidentifiedbasidiomycete growing on wood in French Guiana by Sergej Buchet in 2002,provided to Bayer Healthcare AG, and selected for fermentation in orderto provide extracts that are suitable for natural products screening. OnYMG agar at 23° C., the culture attained about 10 mm diameter after 10days of incubation. The mycelium at first appeared velvety and white,but soon attained a strong yellowish color. The occasional presence ofclamp connections revealed that the fungus belongs to the Basidiomycota.After 5 days of incubation, conidiogenous cells appeared in abundance onthe vegetative hyphae, showing polyblastic, sympodial conidiogenesis,producing subglobose hyaline conidia, averaging 5-6×2.5-3 μm in size.These characteristics were found to be largely in agreement with thedata reported by Shirouzu et al (Persoonia 23, 16-34, 2009). The LSUnucrDNA sequence of this strain FU50088 is included here as sequence<SEQ ID NO: 1>.

The strain was studied in comparison with an authentic strain ofDacryopinax spathularia, CBS 197.63, originating from Africa, which wasobtained from the Centrallbureau voor Schimmelcultures, Utrecht, TheNetherlands. Its morphological characteristics, as well as its secondarymetabolite production were largely in accordance with that of strainFU50088. Furthermore, a high degree of homology was observed between the5.8S/ITS nrDNA and 28S nrDNA sequences of the two aforementioned strainsand reference DNA sequence data that had been published on the Internetby specialists in the taxonomy and phylogeny of Basidiomycota, under thename of Dacryopinax spathularia or synonyms thereof. Therefore, strainFU50088 was identified to belong to the species Dacryopinax spathulariaby morphological, molecular phylogenetic and chemotaxonomic methodologyand is referred herein as this species.

The reference strain Dacryopinax spathularia CBS 197.63, collected fromBangui, Central African Republic, isolated by J. Boidin and depositedwith CBS in April 1963, resembled Dacryopinax spathularia strain FU50088in its growth and morphological characteristics. However, itspigmentation was not as intense, and even in aged cultures, the myceliaonly turned pale yellow. The conidia were subglobose to ovoid, measuring3-6.5 (−8)×2.5-4 μm. The LSU nucrDNA sequence of this reference strainCBS 197.63 is included here as sequence <SEQ ID NO: 2>.

Three other strains that were not assigned to the genus Dacryopinax butare members of family Dacrymycetaceae as well were obtained from publicculture collections, studied and found to produce the compounds of theinvention. Their history and characteristics are given below:

Ditiola nuda strain CBS 173.60 was isolated in Shirokane, Tokyo, Japan,from a petiole of the plant Shiia sieboldii according to the informationprovided in the CBS catalogue and deposited with CBS by K. Tubaki in1960. The strain showed similar growth characteristics to Dacryopinaxspathularia FU50088 and like those of the latter strain; its conidiameasured 6-5×2.5-3 μm. The LSU nucrDNA sequence of Ditiola nuda strainCBS 173.60 is included here as sequence <SEQ ID NO: 3>.

Ditiola radicata strain CBS 126.84 was isolated from sporocarps growingon gymnosperm wood collected in August 1982 in Canada, Alberta, BanffNational Park, C Level Cirque Trail, by Keith A. Seifert and depositedwith CBS in 1984. The strain showed similar growth and morphologicalcharacteristics to Dacryopinax spathularia FU50088, but had smallerconidia (4-5×1.5-2 μm). The LSU nucrDNA sequence of Ditiola radicatastrain CBS 126.84 is included here as sequence <SEQ ID NO: 4>.

Ditiola pezizaeformis strain ATCC13299 was originally deposited withATCC as Femsjonia luteo-alba. The strain had been used in an U.S. Pat.No. 2,974,044 and claimed to be a producer of carotenoids. However,according to the current taxonomy, Femsjonia luteo-alba is a synonym ofthe valid, internationally accepted name, Ditiola pezizaeformis, asreported by Reid (A monograph of the British Dacrymycetales.Transactions of the British Mycological Society 62 (1974): 433-494) andin accordance with current entries in Mycobank and other taxonomicdatabases and monographs of Basidiomycetes. The strain ATCC13299 alsoshowed similar growth and morphological characteristics to strainFU50088, and its conidia were elongate-ellipsoid to subglobose,5-6.5×1.5-2 μm. The LSU nucrDNA sequence of Ditiola pezizaeformis strainATCC13299 is included here as sequence <SEQ ID NO: 5>.

Dacryopinax spathularia strain FU50088 has been deposited under theBudapest Treaty at BCCM/MUCL, Mycothèque de l'Université catholique deLouvain, Place Croix du Sud 3, B-1348 Louvain-la-Neuve, Belgium, underthe designation number MUCL 53181 on Oct. 11, 2010.

Other strains which produce the compounds of the invention have alsobeen deposited under the Budapest Treaty at BCCM/MUCL: Dacryopinaxspathularia, CBS 197.63 under the designation number MUCL 53182 on Oct.11, 2010, Ditiola radicata, CBS 126.84 under the designation number MUCL53180 on Oct. 11, 2010, Ditiola nuda, CBS 173.60 under the designationnumber MUCL 53179 on Oct. 11, 2010, and Femsjonia luteo-alba Fr.1849,ATCC13299 under the designation number MUCL 53500 at May 19, 2011.

Surprisingly the compounds of the invention e.g. compounds of theformula I exhibit a strong, long term inhibitory activity againstorganisms involved in spoilage of pharmaceutical nutraceutical,nutritional, cosmeceutical, and/or cosmetic preparations orcompositions. Said compounds are especially useful against acidophilicspoilage yeasts, which are involved in spoiling or deterioration ofbeverages. Even more surprisingly these compounds are able to inhibitthe growth of thermophilic molds, which are difficult to control withstandard sterilizing and/or pasteurizing processes.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1: Atom numbering of the compounds of the invention for signalassignments of analytical processes.

FIG. 2: Typical HPLC-MS of an extract of FU50088 (MUCL 53181) producedfollowing the example 1B Fermentation c) 200 l fermentation; CPreparation of extracts c) Preparation of a sedimentation product.Adjustment of signals according the “Adapted method” of Example 3. Thenumbers in brackets “[.]” represent the corresponding compound in Table1.

FIG. 3: Typical HPLC-ELSD chromatogram of an extract of Ditiolapezizaeformis strain ATCC13299 (MUCL 53500), peak annotation accordingto Table 16 below.

FIG. 4: Typical HPLC-MS of an extract [X8] obtained from Dacryopinaxspathularia strain FU50088 (MUCL 53181) following example 8D),annotation of signals according the “Improved method” of Example 8C),for details see Table 24A below.

APPLICATIONS & DEFINITIONS

The general expressions, within the present disclosure, preferably havethe following meaning, where in each embodiment one, more than one orall more general expressions may, independently of each other, bereplaced with the more specific definitions, thus forming special, e.g.preferred, embodiments of the invention, respectively:

Preferably, the compounds of the formula I are natural compounds, thatis, compounds that are present in and can be isolated or extracted fromnatural sources (especially those mentioned in detail above and below)without chemical synthesis steps (though they may also be prepared ormodified by chemical synthesis, e.g. acylated or the like), or bemodified by certain downstream processing procedures (e.g. permethylatedunder influence of acidic methanol) and are thus present as extracts orpurified components of extracts, and not derivatives only obtainable bychemical synthesis.

They can also be present and used as part of an extract which isobtainable by extracting a fungus or a part from an appropriate fungusof the genus Dacryopinax.

“Substantially” means preferably that the corresponding impurities arepresent only in trace amounts, e.g. in less than 5% by weight, less than4% by weight, less than 3% by weight, less than 2% by weight, less than1% by weight, less than 0.5% by weight or less than 0.2% by weight, inrelation to the complete weight of the corresponding dry extract orcompound of the formula I or mixture of compounds of the formula I.

In the context of the present invention, the terms “essentially consistsof” or “essentially consisting of” mean that the total weight share is90 wt. % or more, preferably 95 wt. % or more, more preferably 98 wt. %or more, most preferably 99 wt. % or more, in each case based on thetotal amount used. For example, a “mixture essentially consisting of”means that the total amount of the constituents as defined in therespective case is 90 wt. % or more, preferably 95 wt. % or more, morepreferably 98 wt. % or more, most preferably 99 wt. % or more, in eachcase based on the total weight of the mixture

The term “Glycolipid” can be replaced with “glycosylated fatty acid” aswell, where it is used with regard to the compounds of the formula I.

“A compound of the formula I” or “compound(s) of the formula I” canrefer to one or more compounds of the formula I, that is one compound ora mixture of compounds of the formula I, or to the USE of a compound ofthe formula I, where reference to compound(s) of the formula I alwaysincludes the compound(s) as such or in the form of a salt (especially aphysiologically, that is, e.g., pharmaceutically, nutraceutically orcosmetically) acceptable salt, a solvate and/or a tautomer thereof, orin the lactone form. In all cases this means that either only onecompound (in substantially pure form or as a direct extract or a furtherenriched extract) or a mixture of two or more compounds of the formula I(which mixture is preferred) can be present, e.g. in an extract orpharmaceutical, nutraceutical or cosmetical formulation according to theinvention, or that it or they can be of use according to the invention.

The compounds of the formula I may also be esterified at their freecarboxyl group shown in formula I on the right hand side with alcohols,e.g. alcohols with 1 to 10 carbon atoms, such as alkanols, e.g.C₁-C₇alkanols, such as methanol or ethanol, phenyl-C₁-C₄alkanols, suchas benzyl alcohol, or the like. Preferred are the compounds notesterified at the carboxyl group in formula I on the right hand side.

Preferably, the total weight share of the compound or all compounds ofthe formula I in an extract or mixture of compounds of the formula I ora purified compound of the formula I that is of use according to theinvention in the final extract, mixture or compound (direct or furtherenriched) is in the range from 0.01% to 100% by weight, more preferablyfrom 1% to 100% or to 99% by weight, in another embodiment from 5% to100% or to 99% by weight, or from 20% to 100% or to 95% by weight, ore.g. from 50% to 100% or to 90% by weight.

Wherever used in the invention “%” e.g. percent is defined by the weightportion of the part of interest of the total weight, e.g. % is meant as% by weight; except where otherwise explicitly defined.

For the purpose of the invention the term “carbohydrate” is used inconformity with the IUPAC recommendations (Pure and Applied Chemistry,1995, 67, 1307). The term “carbohydrate having 3 to 30 (preferably 6 to18) carbon atoms bound via one of its oxygen atoms” especially refers tomono, oligo- or polysaccharidyl moieties bound via one of their oxygenatoms. The carbohydrates forming the basis for such moieties include,but are not limited to, monosaccharides, disaccharides, furtheroligosaccharides, or polysaccharides.

Monosaccharide for example includes, but is not limited to, aldotriosessuch as glyceraldehyde, ketotrioses such as dihydroxyacetone,aldotetroses such as erythrose and threose, ketotetroses such aserythrulose, aldopentoses such as arabinose, lyxose, ribose and xylose,and desoxypentoses such as deoxyribose; ketopentoses such as ribuloseand xylulose; hexoses, especially aldohexoses such as allose, altrose,galactose, glucose, gulose, idose, mannose and talose, or ketohexosessuch as fructose, psicose, sorbose and tagatose, or desoxyhexoses suchas rhamnose, cymarose, fucose, 2-desoxyglucose or 2-deoxygalactose;heptoses such as mannoheptulose, sedoheptulose; octoses such asoctolose, 2-keto-3-deoxy-manno-octonate; nonoses such as sialoseallose.

Disaccharides for example include, but are not limited to, trehalose,sucrose, kojibiose, sophorose, nigerose, laminaribiose, maltose,cellobiose, isomaltose, gentiobiose, lactose, melibiose, neohsperidose,rutinose, primeverose, sambubiose, xylobiose, lathyrose and mannobiose.

Oligosaccharides for example include, but are not limited to, raffinose,nystose, panose, cellotriose, maltotriose, maltotetraose, xylobiose,galactotetraose, isopanose, cyclodextrin (alpha-CD) orcyclomaltohexaose, beta-cyclodextrin (beta-CD) or cyclomaltoheptaose andgamma-cyclodextrin (gamma-CD) or cyclomaltooctaose. Polysaccharides forexample include, but are not limited to, xylan, mannan, galactan,glucan, arabinan, pustulan, gellan, guaran, xanthan, and hyaluronan.Some examples include, but not limited to, starch, glycogen, cellulose,inulin, chitin, amylose and amylopectin.

In the case of di-, tri- and oligo-saccharides the bonds between thecarbohydrate subunits may include various possible types, e.g.preferably in the form of glycosidic connections of the 1→2, 1→3, 1→4and 1→6 types, in particular the glycosidic connections are of the 1→2type.

Especially preferred are trisaccharide carbohydrate moieties, especiallyof the formula

wherein the rings A, B and C are monosaccharide moieties eachindependently from the others with 5 or 6 ring members, wherein one ormore of the hydroxyl groups may be acylated or etherified.

Preferably the carbohydrate moieties without substitutents resultingfrom acylation or etherification have 15 to 18 carbon atoms and they areespecially selected from the hexapyranosyl-pentapyranosyl-pentapyranosidtype such asbeta-D-glucopyranosyl-(1→2)-beta-D-xylopyranosyl-(1→2)-beta-D-xylopyranosidor the hexapyranosyl-pentapyranosyl-hexapyranosid type such asbeta-D-glucopyranosyl-(1→2)-beta-D-xylopyranosyl-(1→2)-beta-D-glucopyranosid.

The carbohydrates may carry one, more or all hydroxyl groups in modifiedform, e.g. as etherified hydroxyl or especially esterified hydroxyl asdefined below, respectively, for example in a form acylated by aC₂-C₁₀-alkanoic acid, e.g. acetylated, e.g. mono- or di or tri- ortetra-acetylated, form. A particularly preferred modified form isrepresented by those compounds of the formula I which have one or morehydroxyl groups in the carbohydrate moiety that is or are acylated by anisovaleryl (3-methyl-butanoyl) moiety—these compounds are novel and thusalso as such form an invention embodiment.

Individual compounds of formula I with an acyl substituent with morethan 2 carbon atoms, such as (and preferably) an isovaleryl substituent(and preferably one single isovaleryl substituent), in the carbohydratemoiety R typically exhibit a stronger antimicrobial activity,particularly against yeasts and molds, especially against yeasts andmolds of relevance regarding food, beverage and/or cosmetic spoilage,and/or a broader activity spectrum than the corresponding compounds withan acetyl substituent in the carbohydrate moiety R.

Further esters may be acetates; propionates; butyrates; isobyturates;valerates such as n-pentanoate) or 2-methyl butyrate, or the unsaturatedderivatives such as but not limited to 2-methyl-2-butenoate (e.g.angeloate or tiglate), 3-methyl-2-butenoate or 3-methyl-3-butenoate(senecioate), or hydroxylated derivatives such as 2-methyl-3-hydroxybutyrate or 2-hydroxymethyl butyrate; or hexenoates such as n-hexanoate(caproate), isohexanoates such as but not limited to 2-methylvalerate,3-methylvalerate, 4-methylvalerate, 2,3-dimethyl butyrate, or theunsaturated derivatives e.g. 2-ethyl-2-butyrate, 2-methyl-2-pentenoate,4-methyl-2-pentenoate; or aminoacyl, e.g. alanyl, cysteinyl, aspartyl,glutamyl, phenylalanyl, glycyl, histidyl, isoleucyl, lysyl, leucyl,methionyl, asparaginyl, pyrrolysinyl, prolyl, glutaminyl, arginyl,seryl, threonyl, selenocysteyl, valyl, tryptophanyl or tyrosinyl. Theacylated forms may preferably be natural products, but they can also beproducts of chemical or enzymatic acylation, e.g. using active forms ofthe acids and, where required to avoid reaction of other functionalgroups, introduction and, especially to obtain the final product,removal of protecting groups (“Pg”).

The protection of such functional groups by such protecting groups(“Pg”), the protecting groups themselves, and their removal reactionsare described for example in standard reference works, such as J. F. W.McOmie, “Protective Groups in Organic Chemistry”, Plenum Press, Londonand New York 1973, in T. W. Greene and P. G. M. Wuts, “Protective Groupsin Organic Synthesis”, Third edition, Wiley, New York 1999, in “ThePeptides”; Volume 3 (editors: E. Gross and J. Meienhofer), AcademicPress, London and New York 1981, in “Methoden der organischen Chemie”(Methods of organic chemistry), Houben Weyl, 4th edition, Volume 15/I,Georg Thieme Verlag, Stuttgart 1974, in H.-D. Jakubke and H. Jescheit,“Aminosäuren, Peptide, Proteine” (Amino acids, peptides, proteins),Verlag Chemie, Weinheim, Deerfield Beach, and Basel 1982, and in JochenLehmann, “Chemie der Kohlenhydrate: Monosaccharide and Derivate”(Chemistry of carbohydrates: monosaccharides and derivatives), GeorgThieme Verlag, Stuttgart 1974. Especially preferred protecting groupsare hydroxyl protecting groups, such as tert-butyldimethylsilyl, methyl,methoxymethyl, or trityl.

The chemical acylation can take place with the corresponding acid assuch or preferably in the form of a reactive derivative. Reactive (oractive) derivatives used as such include the halogenides, e.g.chlorides, or nitrophenyl esters, e.g. the 2,4-dinitrophenyl esters, oracid anhydrides (symmetric or e.g. with acetic acid) of the carboxygroups of the acids to be reacted.

For in situ formation, customary coupling agents may be applied. Suchreagents are known to the person skilled in the art and can be deducedconveniently from many sources, e.g. Aldrich ChemFiles—Peptide Synthesis(Aldrich Chemical Co., Inc., Sigma-Aldrich Corporation, Milwaukee, Wis.,USA) Vol. 7 No. 2, 2007 (seehttp://www.sigmaaldrich.com/etc/medialib/docs/Aldrich/Brochure/al_chemfile_v7_n2.Par.0001.File.tmp/al_chemfile_v7_n2.pdf).Among the possible coupling agents for amide and ester bond synthesisthe following may be mentioned:

Triazoles, uronium or hexafluorophosphonium derivatives, e.g.1-hydroxy-benzotriazole (HOBt), Carbodiimides, e.g.dicyclohexylcarbodiimide, active ester forming agents, e.g.2-mercaptobenzothiazole (2-MBT), azide forming agents, e.g. diphenylphosphoryl azide, acid anhydrides, such as propane phosphonic acidanhydride, acid halogenation agents, e.g.1-chloro-N,N,2-trimethyl-1-propenylamine, or the like, or mixtures oftwo or more such agents.

While the compounds of the formula I are preferably obtained byextraction in the form of extracts from natural sources or in furtherenriched or purified from such extracts (see below), they can also beobtained by chemical synthesis methods.

For example, the compounds may be synthesized chemically e.g. by aconvergent strategies. The glycoside part and the unbranched long-chainα-hydroxy carboxylic acid part of the molecules are build up separately,with the hydroxyl groups and the carboxylic acid moieties beingprotected by suitable protecting groups. Afterwards, both buildingblocks are connected via building a glycosidic linkage using methodsdescribed in the scientific literature. Finally, removal of theprotecting groups will lead to the desired compounds.

The following Reaction schemes provides an Example of a possiblesynthesis pathway:

Synthetic methods for glycosylation reactions—including protection,activation and deprotection strategies—are described, e.g., in thefollowing literature:

-   J. McMurry; Organic Chemistry, 5th ed.; Brooks/Cole; 2000, 1031;    D E. Levy, P. Fügedi; The organic chemistry of sugars; Taylor &    Francis, 2006, 181-197; S. Bufali, P. Seeberger, Org. React. 2006,    68, 303; G.-J. Boons, K. J. Hale, Organic synthesis with    carbohydrates. Blackwell Publishing, 2000; R. R. Schmidt, J. Michel,    Angew. Chem. Int. Ed. Engl. 1980, 19, 731-732; X. M. Zhu, R. R.    Schmidt, Angew. Chem. Int. Ed. 2009, 48, 1900-1934; R. R. Kale et    al, Angew. Chem. Int. Ed. 2008, 47, 1265-1268; N. Miguel, S.    Vignando, G. Russo, L. Lay, Synlett 2004, 2, 341-343; W. Koenigs, E.    Knorr, Chem. Ber. 1901, 34, 957-981; Fraser-Reid, B.; Tatsuta, K.;    Thiem, J., Hrsg., Glycoscience—Chemistry and Chemical Biology,    Springer: Berlin, (2001); Lindhorst, T. K., Essentials of    Carbohydrate Chemistry and Biochemistry, Wiley-VCH: Weinheim,    (2000); Bochov, A. F.; Zaikov, G. E., Chemistry of the O-Glycosidic    Bond: Formation and Cleavage, Pergamon Press: Oxford, (1979);    Fraser-Reid, B.; Wu, Z.; Udodong, U. E.; Ottosson, H., J. Org.    Chem., (1990) 55, 6068-6070; Lemieux, R. U.; Morgan, A. R., Can. J.    Chem., (1965) 43, 2190-2198; Sinay, P., Pure Appl. Chem., (1991) 63,    519-528 Toshima, K.; Tatsuta, K., Chem. Rev., (1993) 93, 1503-1531;    Evans, W. L.; Reynolds, D. D.; Talley, E. A., Adv. Carbohydr.    Chem., (1951) 6, 27-81

Synthetic methods for dihydroxylation reactions are described, e.g., inthe following literature:

-   R. Brückner: Reaktionsmechanismen, 2. Aufl, Spektrum Verlag,    Heidelberg/Berlin 2003, 750-758; M. H. Junttila, O. E. O. Hormi, J.    Org. Chem., 2004, 69, 4816-4820; M. H. Junttila, O. O. E. Hormi, J.    Org. Chem., 2009, 74, 3038-3047; B. M. Choudary, N. S. Chodari, K.    Jyothi, M. L. Kantam, J. Am. Chem. Soc., 2002, 124, 5341-5349; G. M.    Mehltretter, S. Bhor, M. Klawonn, C. Döbler, U. Sundermeier, M.    Eckert, H.-C. Militzer, M. Beller, Synthesis, 2003, 295-301; L. C.    Branco, C. A. M. Afonso, J. Org. Chem., 2004, 69, 4381-4389; Krauch,    H.; Kunz, H., Reaktionen der Organischen Chemie, 6. Aufl.; Hüthig:    eidelberg, (1997); S. 434-436; Hudlicky, T.; Fan, R.; Luna, H.;    Olivo, H.; Price, J., Pure Appl. Chem., (1992) 64, 1109-1113;    Jacobsen, E. N., Acc. Chem. Res., (2000) 33, 421-431; Kolb, H. C.;    VanNieuwenhze, M. S.; Sharpless, K. B., Chem. Rev., (1994) 94,    2483-2547.

Synthetic methods for reactions connecting two building blocks viadouble bond generation are described, e.g., in the following literature:

-   Ivin, K. J.; Mol, J. C., Olefin Metathesis and Metathesis    Polymerization, Academic Press: New York, (1997); Grubbs, R. H.,    Handbook of Metathesis, Wiley-VCH: Weinheim, (2003); Bd. 1-3;    Fürstner, A.; Langemann, K., Synthesis, (1997), 792-803; Fürstner,    A., Angew. Chem., (2000) 112, 3140-3172; Blakemore, P. R., J. Chem.    Soc., Perkin Trans. 1, (2002), 2563-2585; Staden, L. F., van;    Gravestock, D.; Ager, D. J., Chem. Soc. Rev., (2002) 31, 195-200;    Wittig, G., Angew. Chem., (1980) 92, 671-675; Schlosser, M.;    Christmann, K., Synthesis, (1969), 38-39; Maryanoff, B. E.;    Reitz, A. B., Chem. Rev., (1989) 89, 863-927; Murphy, P. J.;    Brennan, J., Chem. Soc. Rev., (1988) 17, 1-30; Boutagy, J.; Thomas,    R., Chem. Rev., (1974) 74, 87-99; Clayden, J.; Warren, S., Angew.    Chem., (1996) 108, 261-291; Brückner, R., Reaktionsmechanismen, 2.    Aufl.; Spektrum: Heidelberg, (2003); Ager, D. J., Synthesis, (1984),    384-398; Mukaiyama, T.; Asami, M., Top. Curr. Chem., (1985) 127,    133-167.

Further, the present glycolipid compounds of the formula I comprise allstereoisomers, such as those which may exist due to asymmetric carbonson the various substituents, including enantiomeric forms anddiastereomeric forms. Individual stereoisomers of the glycolipidderivatives of the present invention may, for example, be substantiallyfree of other isomers, or may be admixed, for example, as racemates orwith all other, more than one other, or two to less than all otherselected stereoisomers, e.g. diastereomers.

Especially the vicinal dihydroxy group in the fatty acid part is in oneembodiment of the invention to be understood as syn and/or anticonfigurated.

To the extent that compounds the formula I and salts thereof may existin their tautomeric form, all such tautomeric forms are contemplatedherein as part of the present invention embodiments.

As the final carboxyl group of the carboxylic acid chain may also form alactone with one of the hydroxyl groups present on the rest of amolecule of the formula I, compounds of the formula I may also bepresent in the lactone form, either purely or in admixture with the openchain form.

The salts of compound(s) of the formula I are especially physiologicallyacceptable salts, that is, salts that have no disturbing toxical,allergenic and/or mutagenic properties on human or animal cells. Suchsalts can be selected from those known in the art, e.g. using calcium,sodium, magnesium, or ammonium as counterions of the carboxylic group orthe salts mentioned below.

Where salt-forming groups (e.g. acidic groups, such as carboxylic acidgroups, or basic groups, such as amino or imino groups) are presentwithin them, the glycolipid compounds of the formula I may be in thefree form or in the form of salts. The term “salt(s)”, as employedherein, denotes acidic and/or basic salts formed with inorganic and/ororganic acids and bases. In addition, when a compound of the formula Icontains both a basic moiety and an acidic moiety, “inner salts” may beformed and are included within the term “salt(s)” as used herein.Pharmaceutically or nutraceutically or cosmetically acceptable (i.e.,non-toxic, physiologically acceptable) salts are preferred, althoughother salts are also useful, e.g., in isolation or purification stepswhich may be employed during preparation. Salts of compounds of theformula I may be formed, for example, by reacting a compound of theformula I with an amount of acid or base, such as an equivalent amount,in a medium such as one in which the salt precipitates or in an aqueousmedium followed by lyophilisation or followed by the addition of a watermiscible organic solvent. Also ion exchangers can be used to form saltsfrom free forms or free forms from salts of a compound of the formula I.“Free form” refers to “form without salt-forming counterions”, e.g. innon-salt form.

Where two active groups with different charge are present, also internalor zwitterionic salts can be formed.

Where the compounds of the formula I (or glycolipids of the formula I orthe like) are mentioned in the present disclosure, this also comprisesthe corresponding (especially physiologically acceptable) salts thereof,also where not explicitly stated, as well as the esters, as well as thelactones, or mixtures of two or more of these forms.

The compounds of the formula I which contain an acidic moiety (e.g.carboxyl (—COON) groups) may form salts with a variety of organic andinorganic bases. Exemplary basic salts include ammonium salts, non-toxicmetal salts derived from metals of groups Ia, Ib, IIa and IIb of thePeriodic Table of Elements, e.g. alkali metal salts such as sodium,lithium, or potassium salts, alkaline earth metal salts such as calciumor magnesium salts, or salts with other metals, such as zinc, salts withorganic bases (for example, organic amines) such as unsubstituted orhydroxy-substituted mono-, di- or tri-alkylamines, especially mono-, di-or tri-lower alkylamines, or quaternary ammonium compounds, for examplewith alkyl amines, e.g. t-butyl amine, N-methyl-N-ethylamine,diethylamine, triethylamine, mono-, bis- or tris-(2-hydroxy-loweralkyl)amines, such as mono-, bis- or tris-(2-hydroxyethyl)amine,2-hydroxy-tert-butylamine or tris(hydroxymethyl)methylamine,N,N-di-lower alkyl-N-(hydroxy-lower alkyl)-amines, such asN,N-dimethyl-N-(2-hydroxyethyl)-amine or tri-(2-hydroxyethyl)-amine, orN-methyl-D-glucamine; or cyclic amines such as piperidine, N-lower alkylpiperidine e.g. N-methyl-piperidine, piperazine, or quaternary ammoniumsalts formed via common processes out of the above define amines, suchas tetrabutylammonium salts, or with benzathines, dicyclohexylamines,N-methyl-D-glucamines, N-methyl-D-glucamides, purines, caffeine,theobromine, hydrabamine, choline, betaine, or salts with amino acidssuch as arginine, lysine, histidine and the like. Also salts withsalt-forming pharmaceutical and/or nutraceutical carrier materials arepossible and encompassed by the invention.

Isolation

In order to obtain the compounds of the formula I, as such or comprisedin an extract, preferably the desired substances of the formula I areisolated from natural sources, either with subsequent chemicalmodification (e.g. acylation) or preferably without such chemicalmodification.

The purpose of the extraction and especially isolation step is to retainthe desired substances. Desired substances in the present context areany substances that directly or indirectly contribute to thepreservative properties of the composition, with the proviso that one ormore compounds of the formula I are also included. The isolation can beperformed by isolating or separating the one or more compounds of theformula I according to chemical and/or physical properties. Examples ofchemical properties include affinity for one or more compounds andchemical stability. Examples of physical properties include mass orsize, charge, solubility, polarity, distribution, absorption tosurfaces, melting point, and the like.

Natural compounds of the formula I, or extracts comprising one or morethereof, for USE in or according to the present invention are isolatedfrom one or more cultures, especially liquid cultures, of mushrooms ofthe genera listed above or below, e.g. with the genetic characteristicsprovided in detail below.

By the term “extract”, either a direct extract (in liquid or preferablydried form), e.g. obtained as described below, or preferably a furtherenriched extract (obtainable e.g. by one or more further purificationsteps after extraction, e.g. chromatography, for example as describedbelow) containing one or more, preferably two or more compounds of theformula I is meant.

The compound(s) of the formula I in the form of an extract and extractsaccording to the invention can be obtained especially preferably byextraction of liquid cultures, especially liquid or solid mycelialcultures, of mushrooms of the genus Dacryopinax, e.g. mushrooms or partsthereof of the species Dacryopinax, mushrooms of the genus Ditiola, e.g.mushrooms or parts thereof, and/or mushrooms of the genus Femsjonialuteo-alba, e.g. mushrooms or parts thereof, especially the species andmore especially the deposited strains as defined above.

Extracts according to the invention or useful according to the inventionmay be manufactured according to any suitable process, preferablycomprising extraction of one or more compounds of the formula I. Theterm “extract” wherever used also includes precipitates, e.g.manufactured as described below.

For example, the extraction of one or more compounds and/or mixture ofcompounds of the formula I from a cultured mushroom (especially fromsubmerged mycelial culture) or mushroom part of the genera mentionedabove by means of a lipophilic (preferably non-aqueous) solvent.

Extraction thus may take place with a non polar or weakly polar (meaningless polar than water) solvent or solvent mixture, meaning that thepreferred obtainable or obtained extracts according to the invention arelipophilic extracts.

Preferably, the polarity is defined by an E_(T)(30) value of 56 kcal/molor lower (at 25° C. and 1 bar), e.g. of 52 kcal/mol or lower (water hasan E_(T)(30) of 63.1). The E_(T)(30) method is based on a methodpublished by Reichart et al. and makes use of the stabilisation of theground state of the betaine dye2,6-diphenyl-4-(2,4,6-triphenyl-1-pyridinio)phenolate, CAS No10081-39-7, in apolar solvents leading to a higher energy for thetransition from the ground state (HOMO) to the first excited state(LUMO) of the molecule (see K. Dimroth, J Lieb Ann d Chemie (1963)661(1): 1-37, DOI 10.1002/jlac.19636610102).

Examples of appropriate solvents are organic solvents (two or more ofwhich can also be mixed), e.g. a ketone or an ester, such as acetoneand/or ethyl acetate, an ether, e.g. a cyclic ether such as dioxane,and/or (also in a specific embodiment) an alcohol e.g. ethanol, and/or aliquid or superfluid gas, especially superfluid CO₂.

Alternatively, the extract may be obtained by bringing a culturesupernatant to a slightly alkaline pH, e.g. by adding an alkalimetalhydroxide, such as sodium or potassium hydroxide, separating of anysolid material, e.g. the mycelia or other solid components, e.g. bymicrofiltration, acidifying the filtrate by addition of an acid, e.g. anorganic or inorganic acid, such as a hydrohalogenide, such ashydrochloride, to an appropriate pH, e.g. lower than the pKa (which may,for compounds of the formula I, be assumed to lie in the range of about4.0 to 5.0, e.g. 4.2 to 4.5), removing the supernatant from an obtainedprecipitate (which comprises the compounds of the formula I) andoptionally washing the precipitate and/or extracting the compounds ofthe formula I at an appropriate pH into a less polar solvent, e.g. oneas mentioned above. This process (also leading to what is called an“extract” in the present disclosure) is especially preferred as it leadsto high yield and helps to avoid the use of solvents, thus being botheconomically and ecologically advantageous.

The addition according to the use or method of the invention preferablytakes place by mixing the resulting extract or isolated compound(s) ofthe formula I into such a material or by impregnating or coating it withthe compound(s) of the formula as such or in an appropriate (e.g.liquid) composition.

For preservative or antimicrobial compositions, further processing stepsmay precede and/or follow, such as drying (e.g. freeze-drying,spray-drying, fluid bed or spouted bed or evaporation), granulation,agglomeration, concentrating (e.g. to syrups, formed via concentrationand/or with the aid of thickeners), pasteurizing, sterilizing, freezing,dissolving, dispersing, filtering, centrifuging, confectioning, and thelike.

The compounds of the formula I have surprisingly been found to showespecially preservative or antimicrobial purposes (the term“antimicrobial” especially referring to treated materials which are nottreated to avoid perishing of themselves but are to be used in a formnot contaminated by microbes, e.g. implants or the like, while the term“preservative activity” also includes antimicrobial activity, but alsoother stabilizing activity, e.g. by emulsification or acidification dueto addition of the compound(s) of the formula Ito perishable goods).

The preservative and antimicrobial properties can conveniently be shownby methods known in the art, e.g. as described below and in theExamples.

In such tests, antimicrobial and preservative activity can be shown.

The term “enhance the stability against microorganisms” refers toinhibiting the growth or killing microorganisms, thus providing amaterial equipped according to the invention with one or more compoundsof the formula I with protection against microbial damage, films ordegradation.

Among the materials to which one or more compounds of the formula I canbe added, the following may be mentioned: A material selected from thegroup consisting of a cosmetic, a home care product, a food, a beverage,a pharmaceutical, a medical device, and an active packaging material.Also semi-finished products or precursors are included, e.g. especiallyin the case of beverages or foods, ready-to-use powders or concentrates.

Food & Beverages

The term “food” sometimes also named “foodstuff” means articles used forfood or (drink) for man or other animals, chewing gum, and articles usedfor components of any such article. The term “food” especially refers tomaterials, usually of plant, animal or other organism origin, thatcomprise body nutrients, such as carbohydrates, fats, proteins, vitaminsand/or minerals, and is ingested and assimilated by the human or animalorganism to produce energy, stimulate growth and maintain life. Usually,food has a rather solid form, but may also be near liquid, e.g. in thecase of yoghurt or the like. “Food” includes a raw, cooked, or processededible substance, ice, or ingredient used or intended for use or forsale in whole or in part for human or animal consumption, or chewinggum.

“Beverage” means a liquid product for drinking, usually including water,which may be consumed to quench thirst, to provide nutrition, forpleasure or relish purposes and/or for other functional purposes (e.g.to administer medicines or other functional materials).

Among the liquids for human or animal consumption those can be mentionedwhich are labelled as juice, drink (including soft drink, such aslemonade), non-alcoholic or alcoholic beverage, and/or cocktail.

“Juice” means the aqueous liquid expressed or extracted from one or morefruits or vegetables, purées of the edible portions of one or morefruits or vegetables, or any concentrates of such liquid or purée.

The use as an agent with preservative properties of a compound orcompounds of the formula I includes also the use in precursor productsof beverages, e.g. concentrates, syrups and/or powders will reconstituteto a beverage in the sense of the invention by the addition of water.

The term “infant formula” means a food which purports to be or isrepresented for special dietary use solely as a food for infants byreason of its simulation of human milk or its suitability as a completeor partial substitute for human milk.

Beverages can be alcoholic and/or non alcoholic, carbonated and/or noncarbonated

Beverages include non-dairy milks, and the like.

Beverages may include water, flavoured water, fortified waters,flavoured beverages, carbonated water, e.g. flavoured seltzer or sodawaters, juices, cola, lemon-lime, ginger ale, and root beer beverageswhich are carbonated in the manner of soft drinks, as well as beveragesthat provide health or wellness benefits from the presence ofmetabolically active substances, such as vitamins, amino acids,proteins, carbohydrates, lipids, or polymers thereof, where suchproducts may also be formulated to contain milk, coffee, or tea (e.g.green tea) or other botanical solids, syrup, diet beverages, carbonatedsoft drinks, fruit juices, e.g. orange juice, grapefruit juice, applejuice, red grape juice, white grape juice, pear juice, concord grapejuice, pineapple juice, pomegranate juice, cranberry juice, passionfruit juice, lime juice, lemon juice, mango juice, guava juice, bananajuice, red and black currant juice, cashew apple juice, cantaloupe melonjuice, apricot juice, blackberry juice, lingonberry juice, dewberryjuice, gooseberry juice, crabapple juice, prune juice, plum juice, kiwijuice, strawberry juice, blueberry juice, red raspberry juice, blackraspberry juice, cherry juice, watermelon juice, peach juice, nectarinejuice, loganberry juice, honeydew melon juice, papaya juice, boysenberryjuice, youngberry juice, rhubarb juice, guanabana juice, acai juice,goji juice, fig juice, elderberry juice, date juice, carambola juice,acerola juice, quince juice, bilberry juice, tangerine juice, fruitcontaining beverages, e.g. fruit drinks which provide the flavor of anyof the e.g. aforementioned fruit juices and contain greater than 0%fruit juice but less than 100% fruit juice, fruit flavored beverages,vegetable juices, e.g. tomato juice, beet juice, carrot juice, celeryjuice, vegetable containing beverages, which provide the flavor of anyof the aforementioned vegetable juices and contain greater than 0%vegetable juice but less than 100% vegetable juice, isotonic beverages,non-isotonic beverages, soft drinks containing a fruit juice, coffee,tea, tea beverages prepared from tea concentrate. extracts, or powders,drinkable dairy products, e.g. drinkable yogurts (drink yoghurt), kefiror buttermilk, hot chocolate, chocolate powders/mixes, drinkable soyproducts, non-diary milks, e.g. coconut milk, alcoholic beverages, e.g.malt beverages, wine, beer, distilled liquors, spirits, sparkling wine,champagne or liqueurs, fruit smoothies, horchata (vegetable and/or ricecomponents made into a beverage), sport drinks, energy drinks, healthdrinks, shakes, protein drinks (e.g. dairy, soy, rice or other),drinkable soy yogurts, low acid beverages as defined in US 21 C.F.R.Part 113. Acidified beverages as defined in US 21 C.F.R. Part 114,nectars, tonics, frozen carbonated beverages, frozen uncarbonatedbeverages, liquid meal replacements, infant formulations, andcombinations or mixtures thereof.

It is also possible to formulate such beverages to contain one or morenutraceuticals. Herein, a nutraceutical is a substance that has beenshown to possess, minimally, either a general or specific health benefitor sense of wellness as documented in professional journals or texts.Nutraceuticals, however, do not necessarily act to either cure orprevent specific types of medical conditions.

Apart from one or more compounds of the formula I, the foods orbeverages may comprise further customary additives for food and/orbeverages.

For the purpose of the invention “additives” in the sense of“sweeteners” are substances used to impart a sweet taste to foods (thisterm in the present paragraph also including beverages) or in table-topsweeteners; “antioxidants” are substances that hinder the oxidation ofcomponents, e.g. avoiding that the material becomes rancid; “colors” aresubstances which add or restore color in a food, and include naturalconstituents of foods and natural sources which are normally notconsumed as foods as such and not normally used as characteristicingredients of food. Preparations obtained from foods and other ediblenatural source materials obtained by physical and/or chemical extractionresulting in a selective extraction of the pigments relative to thenutritive or aromatic constituents are colors within the meaning of thisRegulation; “preservatives” are substances which prolong the shelf-lifeof foods by protecting them against deterioration caused bymicro-organisms and/or which protect against growth of pathogenicmicro-organisms; “antioxidants” are substances which prolong theshelf-life of foods by protecting them against deterioration caused byoxidation, such as fat rancidity and color changes; “carriers” aresubstances used to dissolve, dilute, disperse or otherwise physicallymodify a food additive or a flavouring, food enzyme, nutrient and/orother substance added for nutritional or physiological purposes to afood without altering its function (and without exerting anytechnological effect themselves) in order to facilitate its handling,application or use; “acids” are substances which increase the acidity ofa foodstuff and/or impart a sour taste to it; “acidity regulators” aresubstances which alter or control the acidity or alkalinity of afoodstuff; “anti-caking agents” are substances which reduce the tendencyof individual particles of a foodstuff to adhere to one another;“anti-foaming agents” are substances which prevent or reduce foaming;“bulking agents” are substances which contribute to the volume of afoodstuff without contributing significantly to its available energyvalue; “emulsifiers” are substances which make it possible to form ormaintain a homogenous mixture of two or more immiscible phases such asoil and water in a foodstuff; “emulsifying salts” are substances whichconvert proteins contained in cheese into a dispersed form and therebybring about homogenous distribution of fat and other components;“firming agents” are substances which make or keep tissues of fruit orvegetables firm or crisp, or interact with gelling agents to produce orstrengthen a gel; “flavor enhancers” are substances which enhance theexisting taste and/or odor of a foodstuff; “foaming agents” aresubstances which make it possible to form a homogenous dispersion of agaseous phase in a liquid or solid foodstuff; “gelling agents” aresubstances which give a foodstuff texture through formation of a gel;“glazing agents” (including lubricants) are substances which, whenapplied to the external surface of a foodstuff, impart a shinyappearance or provide a protective coating; “humectants” are substanceswhich prevent foods from drying out by counteracting the effect of anatmosphere having a low degree of humidity, or promote the dissolutionof a powder in an aqueous medium; “modified starches” are substancesobtained by one or more chemical treatments of edible starches, whichmay have undergone a physical or enzymatic treatment, and may be acid oralkali thinned or bleached; “packaging gases” are gases other than air,introduced into a container before, during or after the placing of afoodstuff in that container; “propellants” are gases other than airwhich expel a foodstuff from a container; “raising agents” aresubstances or combinations of substances which liberate gas and therebyincrease the volume of a dough or a batter; “sequestrants” aresubstances which form chemical complexes with metallic ions;“stabilizers” are substances which make it possible to maintain thephysico-chemical state of a foodstuff; stabilizers include substanceswhich enable the maintenance of a homogenous dispersion of two or moreimmiscible substances in a foodstuff, substances which stabilize, retainor intensify an existing color of a foodstuff and substances whichincrease the binding capacity of the food, including the formation ofcross-links between proteins enabling the binding of food pieces intore-constituted food; “thickeners” are substances which increase theviscosity of a foodstuff; “flour treatment agents” are substances, otherthan emulsifiers, which are added to flour or dough to improve itsbaking quality.

Among known preservatives for food and beverages (also named additional(chemical) preservatives herein), the following may be mentioned,without excluding others: benzoic acid, benzoic acid sodium salt,benzoic acid potassium salt, benzoic acid calcium salt, propionic acid,salicylic acid, sorbic acid, sorbic acid sodium salt, sorbic acidpotassium salt, sorbic acid calcium salt, ethyl para-hydroxybenzoate,sodium ethyl para-hydroxybenzoate, propyl para-hydroxybenzoate, sodiumpropyl para-hydroxybenzoate, methyl para-hydroxybenzoate, sodium methylpara-hydroxybenzoate, sulphur dioxide, sodium sulphite, sodium hydrogensulphite, sodium metabisulphite, potassium metabisulphite, calciumsulphite, calcium hydrogen sulphite, biphenyl or diphenyl, orthophenylphenol, sodium orthophenyl phenol, thiabendazole, nisin, natamycin orpimaracin, formic acid, sodium formate, calcium formate, hexamethylenetetramine or hexamine, formaldehyde, dimethyl dicarbonate, sodiumnitrite, potassium nitrite, sodium nitrate, potassium nitrate, aceticacid, sodium acetates, e.g. sodium hydrogen acetate, potassium acetate,calcium acetate, ammonium acetate, lactic acid, propionic acid, sodiumpropinate, potassium propionate, calcium propionate, oric acid, sodiumtetraborate (borax), invertase, lysozyme.

Preferably, however, no such preservatives are added in the embodimentsof the present invention.

The consumables of the present invention, e.g., beverages, may have a pHranging from 1.5 to 10, e.g. from about 1.5 to about 4.6 It is known inthe art that the pH of a beverage may be a factor in maintaining ashelf-stable beverage, as the growth of some microorganisms may behindered under acidic conditions. This, however, is not the case foracidophilic microorganisms such as Lactobacillus, Saccharomyces andCandida which thrive in such an acidic environment. Utilizing thepresent invention allows the composition to maintain microbial stabilityeven in view of these acidophilic microorganisms.

For an acidic beverage (pH<4.6), the acidity of the beverage can beadjusted to and maintained within the recited range by known andconventional methods in the art. For example, the pH can be adjustedusing one or more acidulant(s), also named acidity regulator(s), e.g. asdefined below.

In addition, the use of acidity regulators may assist in microbialinhibition at the same time as maintaining the pH of the beverage.Compositions of the present invention, however, may inherently have adesirable pH without the use of any acidity regulator or othercomponents to modify the pH. Thus, the incorporation of at least oneacidity regulator is optional in compositions of the present invention.

Moreover, the amounts of the acidity regulator(s), which may be presentin the composition according to the present disclosure, are thoseconventionally used in beverage compositions. For example, at least oneacidulant may be present in an amount ranging from about 0.01% to about1% by weight relative to the composition.

An aspect of the invention is directed to preserving a broad range ofbeverage products that possess a pH of less than 7.5, in particular lessthan about 4.6, such as 2.5 to 4.6 against spoilage by yeast, mold and arange of acid tolerant bacteria. Preservation of product can beaccomplished merely through the addition of the chemical agentsdescribed herein, but it is also possible to supplement the action ofthe chemicals with purely physical forms of preservation such asalteration of product temperature, various wavelengths of irradiation,pressure or combinations thereof. In certain exemplary embodiments, thepH of the beverage product comprising the preservative system is e.g.,about 4.6 or less, about 2.5 to about 4.4, about 2.6 to about 4.5.

The acidity regulator(s) may be in an undissociated form or in theirrespective salt form such as potassium, sodium, or hydrochloride salts,or be a mixture, thus forming a kind of buffer for an intended pH. Amongacidity regulators (pH regulators), organic and inorganic acids to beused in adjusting the pH of a composition of the present invention suchas a beverage may be mentioned, e.g. acetic acid, sodium acetates, e.g.sodium hydrogen acetate, potassium acetate, calcium acetate, ascorbicacid, sodium ascorbate, potassium ascorbate, carbon dioxide, sodiumcarbonates incl. sodium hydrogen carbonate (bicarbonate of soda) andsodium sesquicarbonate, potassium carbonates, e.g. potassium hydrogencarbonate, ammonium carbonates, e.g. ammonium hydrogen carbonate,magnesium carbonates, e.g. magnesium hydroxide carbonate (syn. magnesiumhydrogen carbonate), malic acid, fumaric acid, sodium fumarate,potassium fumarate, calcium fumarate, calcium citrates incl. mono, di ortri calcium salts, triammonium citrate, ammoniumferrocitrate, sodiummalates, e.g. sodium hydrogen malate, potassium malate, calcium malates,e.g. calcium hydrogen malate, adipic acid, sodium adipate, potassiumadipate, succinic acid, 1,4-heptonolactone, potassium chloride, calciumchloride, ammonium chloride or ammonia solution, magnesium chloride,stannous chloride, sodium sulphates, e.g. sodium hydrogen sulphate,potassium sulphates, e.g. potassium hydrogen sulphate, calcium sulphate,ammonium sulphate, magnesium sulphate or Epsom salts, copper sulphate,aluminium sulphate, aluminium sodium sulphate, aluminium potassiumsulphate, aluminium ammonium sulphate, sodium hydroxide, potassiumhydroxide, calcium hydroxide, ammonium hydroxide, magnesium hydroxide,calcium oxide, magnesium oxide, sodium ferrocyanide, potassiumferrocyanide, calcium ferrocyanide, dicalcium diphosphate, tartaricacid, sodium tartaric acid, potassium tartaric acid, gluconic acid,glucono-delta-lactone, or mixtures of two or more thereof, may bementioned. Note that the compounds of the formula I, due to theiracid/base properties, can also be used to regulate the pH of acomposition comprising them.

Among the emulsifiers, the following may be mentioned:

lecithins; metatartaric acid, calcium tartrate; alginic acid and thesodium, potassium, ammonium and calcium salts, propane-1,2-diolalginate; agar; Carrageenan; processed eucheuma seaweed; locust beangum; carob gum; guar gum; tragacanth; acacia gum; gum arabic; xanthangum; Karaya gum; Tara gum; Gellan gum; glycerol; Konjac, konjac gum,konjac glucomannane; soybean emicellulose; Cassia gum; polyoxyethylene(8) stearate; polyoxyethylene sorbitan monolaurate, polysorbate 20;polyoxyethylene sorbitan monooleate, polysorbate 80; polyoxyethylenesorbitan monopalmitate, polysorbate 40; polyoxyethylene sorbitanmonostearate, polysorbate 60; polyoxyethylene sorbitan tristearate,polysorbate 65; pectins and amidated pectin; ammonium phosphatides;sucrose acetate isobutyrate; glycerol esters of wood rosins;diphosphates and salts, disodium, trisodium diphosphate, tetrasodiumdiphosphate, dipotassium diphosphate, tetrapotassium diphosphate,dicalcium diphosphate, calcium dihydrogen diphosphate; triphosphates andsalts, pentasodium, pentapotassium; polyphosphates and salts, sodium,potassium, sodium calcium, calcium, sodium aluminium, aluminium;beta-cyclodextrine; cellulose, podered or microcrystalline andderivatives, methyl-, ethyl-, hydroxypropyl-, hydroxypropyl methyl-,ethyl methyl-, carboxy methyl-, crosslinked sodium carboxy methyl-,enzymatically hydrolysed carboxy methyl-; sodium, potassium and calciumsalts of fatty acids; magnesium salts of fatty acids; mono- anddiglycerides of fatty acids; acetic acid esters of mono- anddiglycerides of fatty acids; lactic acid esters of mono- anddiglycerides of fatty acids; citric acid esters of mono- anddiglycerides of fatty acids; tartaric acid esters of mono- anddiglycerides of fatty acids; mono- and diacetyltartaric acid esters ofmono- and diglycerides of fatty acids; mixed acetic and tartaric acidesters of mono- and diglycerides of fatty acids; sucrose esters of fattyacids; sucroglycerides; polyglycerol esters of fatty acids; polyglycerolpolyricinoleate; propane-1,2-diol esters of fatty acids; thermallyoxidised soya bean oil interacted with mono- and diglycerides of fattyacids; sodium stearoyl-2-lactylate; calcium stearoyl-2-lactylate;stearyl tartrate; sorbitan monostearate; sorbitan tristearate; sorbitanmonolaurate; sorbitan monooleate; sorbitan monopalmitate; invertase;silicon dioxide (Silica); magnesium stearate, calcium stearate; oxidizedstarch; acetylated distarch phosphate; starch sodium octenyl succinate;acetylated oxidised starch, or mixtures of two or more thereof.

As anti-oxidants, among others the following may be mentioned:

ascorbic acid and salts, sodium, calcium; fatty acid esters of ascorbicacid; tocopherols, alpha-tocopherol, gamma-tocopherol, delta-tocopherol;propyl gallate; octyl gallate; dodecyl gallate; erythorbic acid, sodiumerythorbate; tertiary-butyl hydroquinone (TBHQ); butylatedhydroxyanisole (BHA); butylated hydroxytoluene (BHT); extracts ofrosemary; 4-hexylresorcinol, or mixtures of two or more thereof.

Such additives may be present in relative amounts, considering thecomplete composition of the food or beverage product concerned, inamounts summing up to from 0.01% up to 90% by weight, e.g. from 0.05% to50% by weight, e.g. from 0.1% to 5% by weight or from 0.2% to 20% byweight.

Cosmetics

The compounds of the formula I, in view of their preservativeproperties, are also useful in supporting or providing preservation ofcosmetics.

The term “cosmetic” is here intended to mean

(1) an article, e.g. a mixture or substance or product, intended to beplaced in contact with the various external parts of the human body oranimal body (epidermis, hair system, nails, lips and external genitalorgans), e.g. which can be rubbed, poured, sprinkled, or sprayed on, orotherwise applied to the human body or any part thereof, including theoral cavity and the teeth, skin and hair,with a view exclusively or mainly to cleaning them, perfuming them,changing their appearance and/or correcting body odors, and/orprotecting them or keeping them in good condition.; and(2) articles intended for use as a component of any such articles;explicitly including soap.

The term cosmetics as used here also includes “personal care products”and “personal hygiene products”, such as menstrual care products,handkerchief tissues and the like.

For example, cosmetic products include but are not limited to:

Creams, emulsions, lotions, gels and oils for the skin (hands, face,feet, etc.); face masks (with the exception of peeling products); tintedbases (liquids, pastes, powders); make-up powders, after-bath powders,hygienic powders, etc.; toilet soaps, deodorant soaps, etc.; perfumes,toilet waters and eau de Cologne; bath and shower preparations (salts,foams, oils, gels, etc.); depilatories; deodorants and anti-perspirants;hair care products, (hair tints and bleaches; products for waving,straightening and fixing); setting products; cleansing products(lotions, powders, shampoos, hand washing products, (hand) disinfectingproducts); conditioning products (lotions, creams, oils); hairdressingproducts (lotions, lacquers, brilliantines); shaving products (creams,foams, lotions, etc.); products for making up and removing make-up fromthe face and the eyes; products intended for application to the lips;products for care of the teeth and the mouth (e.g. gargles, mouthwash ortoothpastes); products for nail care and make-up; products for externalintimate hygiene; sunbathing products; products for tanning without sun;skin-whitening products; anti-wrinkle products, tampons, sanitarytowels, wet wipes, diapers or handkerchiefs.

Depending on the field of application, certain above mentioned cosmeticproducts may also be used in the medical filed, in particular certainwashing products are suitable as disinfecting products, such as handdisinfecting products or instrument disinfecting products.

In all cases, the antimicrobial properties of the compounds of theformula I may provide, as additional benefit in the sense of a bonuseffect, their antimicrobial efficiency to the cosmetic properties of theformulations, although the purely cosmetic use of the correspondingcosmetics is preferably predominant.

The cosmetics may comprise, in relationship to their intended use,various active and inactive ingredients, named “cosmetic additives” inthe following.

Among the cosmetic additives, the following, without limiting the scopeof possible additives, may be mentioned:

“Abrasives” are substances which remove materials from various bodysurfaces or aids mechanical tooth cleaning or improves gloss,“absorbents” are substances which take up water- and/or oil-solubledissolved or finely dispersed substances, “anti-cakings” are substanceswhich allow free flow of solid particles and thus avoids agglomerationof powdered cosmetics into lumps or hard masses, “anti-corrosives” aresubstances which prevent corrosion of the packaging, “anti-dandruffs”are substances which help to control dandruff, “anti-foaming” aresubstances which suppress foam during manufacturing or reduce thetendency of finished products to generate foam, “anti-microbials” aresubstances which help to control the growth of micro-organisms on theskin, “anti-oxidants” are substances which inhibit reactions promoted byoxygen, thus avoiding oxidation and rancidity, “anti-perspirants” aresubstances which reduce perspiration, “anti-plaques” are substanceswhich help to protect against plaque, “anti-seborrhoeics” are substanceswhich help to control sebum production, “anti-statics” are substanceswhich reduce static electricity by neutralising electrical charge on asurface, “astringents” are substances which contract the skin,“bindings” are substances which provide cohesion in cosmetics,“bleachings” are substances which lightens the shade of hair or skin,“bufferings” are substances which stabilize the pH of cosmetics,“bulkings” are substances which reduce bulk density of cosmetics,“chelatings” are substances which react and form complexes with metalions which could affect the stability and/or appearance of cosmetics,“cleansings” are substances which help to keep the body surface clean,“cosmetic colorants” are substances which color cosmetics and/or impartscolor to the skin and/or its appendages (e.g. hair or nails) (e.g. dyesor pigments, e.g. lactoflavin, caramel capsanthin, capsorubin, beetrootred, anthocyanins, bromothymol blue, bromocresol green, acid red,aluminium, magnesium, calcium and zinc stearates); “denaturants” aresubstances which render cosmetics unpalatable, mostly added to cosmeticscontaining ethyl alcohol; “deodorants” are substances which reduce ormask unpleasant body odors, “depilatories” are substances which removeunwanted body hair; “detanglings” are substances which reduce oreliminate hair intertwining due to hair surface alteration or damageand, thus, helps combing; “emollients” are substances which soften andsmooth the skin; “emulsifiers” are substances which promote theformation of intimate mixtures of non-miscible liquids by altering theinterfacial tension; “emulsion stabilizers” are substances which helpthe process of emulsification and improves emulsion stability andshelf-life; “film formings” are substances which produce, uponapplication, a continuous film on skin, hair or nails; “foamings” trapnumerous small bubbles of air or other gas within a small volume ofliquid by modifying the surface tension of the liquid; “foam boosters”are substances which improve the quality of the foam produced by asystem by increasing one or more of the following properties: volume,texture and/or stability; “gel formers” are substances which give theconsistency of a gel (a semi-solid preparation with some elasticity) toa liquid preparation; “hair conditioners” are substances which leave thehair easy to comb, supple, soft and shiny and/or imparts volume,lightness, gloss, etc; “hair dyes” are substances which color hair;“hair fixers” are substances which permit physical control of hairstyle;“hair waving or straighteners” are substances which modify the chemicalstructure of the hair, allowing it to be set in the style required;“humectants” are substances which hold and retain moisture;“hydrotropers” are substances which enhance the solubility of substancewhich is only slightly soluble in water; “keratolytics” are substanceswhich help to eliminate the dead cells of the stratum corneum; “maskingagents” are substances which reduce or inhibit the basic odor or tasteof the product; “moisturing” compounds increase the water content of theskin and helps keep it soft and smooth; “nail conditioners” aresubstances which improve the cosmetic characteristics of the nail;“opacifiers” are substances which reduce transparency or translucency ofcosmetics; “oral care” provides cosmetic effects to the oral cavity,e.g. cleansing, deodorising, protecting; “oxidizers” are substanceswhich change the chemical nature of another substance by adding oxygenor removing hydrogen; “pearlescents” are substances which impart anacreous appearance to cosmetics; “plasticizers” are substances whichsoften and make supple another substance that otherwise could not beeasily deformed, spread or worked out; “preservatives” (additionalpreservatives) are substances which inhibit primarily the development ofmicro-organisms in cosmetics; “propellants” are substances whichgenerate pressure in an aerosol pack, expelling contents when the valveis opened, some liquefied propellants can act as solvents; “reducers”are substances which change the chemical nature of another substance byadding hydrogen or removing oxygen; “refatters” are substances whichreplenish the lipids of the hair or of the top layers of the skin;“refreshers” are substances which impart a pleasant freshness to theskin; “skin conditioners” are substances which maintain the skin in goodcondition; “skin protectors” are substances which help to avoid harmfuleffects to the skin from external factors; “smoothers” are substanceswhich seek to achieve an even skin surface by decreasing roughness orirregularities; “solvents” are substances which dissolve othersubstances; “soothers” are substances which helps lightening discomfortof the skin or of the scalp; “stabilizers” are substances which improveingredients or formulation stability and shelf-life; “surfactants” aresubstances which lower the surface tension of cosmetics as well as aidsthe even distribution of the product when used; “tanning” is a processwhich darkens the skin with or without exposure to UV; “tonics” aresubstances which produce a feeling of well-being on skin and hair; “UVabsorbers” are substances which protect the cosmetic product from theeffects of UV light; “UV filters” are substances which filter certain UVrays in order to protect the skin or the hair from harmful effects ofthese rays; “viscosity controllers” are substances which increase ordecrease the viscosity of cosmetics.

In one embodiment, the formulations can be or comprise or containcosmetic additives such as those conventionally used in cosmeticpreparations, e.g. sunscreens, preservatives, bactericides, fungicides,virucides, cooling substances, insect repellents (e.g. DEET, IR 3225,Dragorepel), plant extracts, antiinflammatory substances, wound healingaccelerators (e.g. chitin or chitosan and its derivatives), film-formingsubstances (e.g. polyvinylpyrrolidones or chitosan or its derivatives),customary antioxidants, vitamins (e.g. vitamin C and derivatives,tocopherols and derivatives, vitamin A and derivatives),2-hydroxycarboxylic acids (e.g. citric acid, malic acid, L-, D- orDL-lactic acid), skin colorants (e.g. walnut extracts ordihydroxyacetone), active ingredients for promoting hair growth (e.g.minoxidil, diphencyprone, hormones, caffeine, finasteride, phytosterolssuch as beta-sitosterol, biotin, or extracts of Cimicifuga racemosa,Eugenia caryophyllata or Hibiscus rosa-sinensis, barley, hops, or riceor wheat hydrolysates), skin care products (e.g. cholesterol, ceramides,pseudoceramides), softening, moisturizing and/or moisture-retainingsubstances (e.g. glycerol or urea), fats, oils, saturated fatty acids,monounsaturated or polyunsaturated fatty acids, alpha-hydroxy acids,polyhydroxy fatty acids or their derivatives (e.g. linoleic acid,alpha-linolenic acid, gamma-linolenic acid or arachidonic acid and theirrespective natural or synthetic esters), waxes or other conventionalconstituents of a cosmetic or dermatological formulation, such asalcohols, polyols, polymers, foam stabilizers, electrolytes, organicsolvents, silicone derivatives or chelating agents (e.g.ethylenediaminetetraacetic acid and derivatives), antidandruffsubstances (e.g. climbazole, ketoconazole, piroctonoleamine, zincpyrithione), hair care products, perfumes, antifoams, dyestuffs,pigments with a coloring action, thickeners (advantageously silicondioxide, aluminium silicates such as bentonites, polysaccharides ortheirderivatives, e.g. hyaluronic acid, guar kernel flour, xanthan gum,hydroxypropyl methyl cellulose or allulose derivatives, particularlyadvantageously polyacrylates such as carbopols, or polyurethanes),surface-active substances, emulsifiers, plant parts and plant extracts(e.g. arnica, aloe, beard lichen, ivy, stinging nettle, ginseng, henna,camomile, marigold, rosemary, sage, horsetail or thyme), animalextracts, e.g. royal jelly or propolis, proteins, protein hydrolysates,yeast extracts, hop and wheat extracts, peptides or thymus extracts.

Among the “preservatives” (additional preservatives) for cosmeticpreparations, the following may be mentioned: benzoic acid, formic acidand their sodium salt; propionic acid, salicylic acid, sorbic acid,other weak acids, e.g. free fatty acids, esters and derivatives thereof,undec-10-enoic acid and their salts; formaldehyde incl. paraformaldehyde; biphenyl-2-ol and its salts; zinc pyrithione; inorganicsulphites and hydrogen-sulphites; chlorobutanol; 4-hydroxybenzoic acidand its salts and esters; 3-acetyl-6-methylpyran-2,4 (3H)-dione(dehydracetic acid) and its salts;3,3′-dibromo-4,4′-hexamethylenedioxydibenzamidine (dibromohexamidine)and its salts (including isethionate); thiomersal; phenylmercuric salts(including borate); hexetidine; 5-bromo-5-nitro-1,3-dioxane; bronopol;2,4-dichlorobenzyl alcohol; triclocarban; 4-chloro-m-cresol; triclosan;4-chloro-3,5-xylenol;3,3′-bis(1-hydroxymethyl-2,5-dioxoimidazolidin-4-yl)-1,1′-methylenediurea(imidazolidinyl urea); poly (1-hexamethylenebiguanide hydrochloride;2-phenoxyethanol; hexamethylenetetramine (methenamine); methenamine3-chloroallylochloride;1-(4-chlorophenoxy)-1-(imidazol-1-yl)-3,3-dimethylbutan-2-one;1,3-bis(hydroxymethyl)-5,5-dimethylimidazolidine-2,4-dione; benzylalcohol; 1-hydroxy-4-methyl-6(2,4,4-trimethylpentyl) 2-pyridone and itsmonoethanolamine salt; 6,6-dibromo-4,4-dichloro-2,2′-methylenediphenol(bromochlorophen); 4-isopropyl-m-cresol; mixture of5-chloro-2-methyl-isothiazol-3(2H)-one and 2-methylisothiazol-3(2H)-onewith magnesium chloride and magnesium nitrate; 2-benzyl-4-chlorophenol(clorophene); 2-chloroacetamide; chlorhexidine and its digluconate,diacetate and dihydrochloride; 1-phenoxypropan-2-ol; alkyl (C12-C22)trimethyl ammonium, bromide; 4,4-dimethyl-1,3-oxizalidine;N-(hydroxymethyl)-N-(dihydroxymethyl-1,3-dioxo-2,5-imidazolidinyl-4)-N′-(hydroxymethyl)urea and chloride; 1,6-Di-(4-amidinophenoxy)-n-hexane (Hexamidine) andits salts (including isethionate and p-hydroxybenzoate); glutaraldehyde(pentane-1,5-dial); 5-ethyl-3,7-dioxa-1-azabicyclo[3.3.0]octane;3-(p-chlorophenoxy)-propane-1,2 diol (chlorphenesin); sodiumhydroxymethylamino acetate (sodium hydroxymethylglycinate); silverchloride deposited on titanium dioxide; benzethonium chloride;benzalkonium chloride, bromide and saccharinate; benzylhemiformal;iodopropynyl butylcarbamate (IPBC) 3-iodo-2-propynylbutylcarbamate;methylisothiazolinone, sodium hexametaphosphate,ethylenediaminetetraacetic acid, peptides such as polylysine, lauricarginate, cultured dextrose, neem oil, eugenol, p-cymene, thymol,carvacrol, linalool, hydroxycinnamic acid, cinnamic acid, cinnamicaldehyde, tea tree oil, fingerroot extract, acai powder, 4-hydroxybenzylisothiocyanate and/or white mustard seed essential oil, ferulic acid, ormixtures of two or more thereof.

Other preserving agents such 1,3-diols which are named in WO 2011/023582and/or benzaldehydes such as those disclosed in WO 2009/000097, orextracts from Scutellaria baicalensis such as those disclosed in KR20030012821 are also understood as preservatives. Preferred areScutellaria baicalensis extracts comprising dimethoxytetrahydroxyflavoneand/or baicaleine (5,6,7-trihydroxyflavone), e.g. as obtainable byextraction with a solvent selected from propylene glycol, glycerine,1,3-butylene glycol, water, ethanol, and mixtures thereof.

The cosmetics according to the invention preferably comprise onlynatural preservatives, or no preservatives are added in view of thepreservative properties of the compound(s) of the formula I.

The invention also comprises cosmetics, especially their use, comprisingbeyond one or more of the compounds of the formula I also “other naturalantimicrobially active agents”, e.g. proteins, corresponding peptidesalone or in combination, natural essential oils or derivatives thereof,such as oil from anis, lemon, orange, grapefruit, rosemary, thyme,lavender, tee tree, citron, wheat, lemon grass, cedar, cinnamon,eucalyptus, peppermint, basil, fennel, menthol, Ocmea origanum, Hydastiscarradensis, Krameria lappacea, Podophyllum spp., Curcuma longa, ormixtures of two or more such oils.

In certain embodiments of the invention, essential oils are used incombination with emollient solvents and AHAs. Essential oils (“EOs”), asdefined herein, are volatile oils obtained from plant or animal sources,or their synthetic equivalents, and are composed of complex mixtures ofseveral constituents as monoterpenes and sesquiterpene hydrocarbons,monoterpene and sesquiterpene; alcohols, esters, ethers, aldehydes,ketones, oxides and the like. Examples of EOs include but are notlimited to: bergamot oil, clary sage oil, sage oil, almond oil,ylang-ylang oil, neroli oil, sandalwood oil, frankincense oil, gingeroil, peppermint oil, lavender oil, jasmine absolute, geranium oilbourbon, spearmint oil, elove oil, patchouli oil, rosemary oil, rosewoodoil, sandalwood oil, tea tree oil, vanilla oil, lemongrass oil,cedarwood oil, balsam oils, tangerine oil, Hinoki oil, Hiba oil, ginkooil, eucalyptus oil, lemon oil, orange oil, thyme oil, savory oil,oregano oil, and sweet orange oil. Botanicals, such as camphor andcinnamon may also be used. Individual constituents (“ICs”) of essentialoils may be natural or entirely or partially synthetic, and include, butare not limited to, l-citronellol, alpha-amylcinnamaldehyde, lyral,geraniol, famesol, hydroxycitronellal, isoeugenol, eugenol, eucalyptol,linalool, citral, thymol, limonene and menthol. Additionally,sesquiterpenoids such as nerolidol, farnesol, bisabolol and apritone mayalso be used in the present invention. Mixtures of one or more EO, oneor more IC, and one or more EO as well as one or more IC, areencompassed by the present invention.

Possible UV filters include but are not limited to:phenylen-1,4-bis-(2-benzimidazyl)-3,3′-5,5′-tetrasulfonic acids;2-phenylbenzimidazol-5-sulfonic acid and corresponding salts;1,4-di(2-oxo-10-sulfo-3-bornylidenmethyl)-benzene and correspondingsalts; 4-(2-oxo-3-bornylidenmethyl)benzenesulfonic acid and its salts;2-methyl-5-(2-oxo-3-bornylidenmethyl)sulfonic acid and its salts;2,2′-methylen-bis-(6-(2H-benzotriazol-2-yl)-4-(1,1,3,3-tetramethylbutyl)-phenol);2-(2H-benzotriazol-2-yl)-4-methyl-6-[2-methyl-3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]disiloxanyl]propyl]-phenol;3-(4-methylbenzyliden)campher; 3-benzylidencampher;4-(tert-butyl)-4′-methoxydibenzoylmethane;2-(4′-diethylamino-2′-hydroxybenzoyl)-benzoic acid methyl ester;terephthalidendicamphersulfonic acid; 4-(dimethylamino)-benzoic acid(2-ethylhexyl)ester; 4-(dimethylamino)benzoic acid amylester;4-ethoxybenzalmalonic acid (2-ethylhexyl)ester;2-hydroxy-4-methoxybenzophenone,2-hydroxy-4-methoxy-4′-methylbenzophenone;2,2′-dihydroxy-4-methoxybenzophenone; 2-ethylhexyl-2-hydroxybenzoate;3-(4-(2,2-bisethoxycarbonylvinyl)-phenoxy)propenyl)-methoxysiloxan/dimethylsiloxan-copolymer;dioctylbutylamidotriazone (INCI: Diethylhexyl-Butamidotriazone);2,4-bis-[5-1(dimethylpropyl)benzoxazol-2-yl-(4-phenyl)-imino]-6-(2-ethylhexyl)-imino-1,3,5-triazine(CAS RN 288254-16-0);4,4′,4″-(1,3,5-triazin-2,4,6-triyltriimino)-tris-benzoic acidtris(2-ethylhexylester) (also:2,4,6-tris-[anilino-(p-carbo-2′-ethyl-t-hexyloxy)]-1,3,5-triazine (INCI:Ethylhexyl Triazone);2,4-bis-{[4-(2-ethyl-hexyloxy)-2-hydroxy]-phenyl}-6-(4-methoxphenyl)-1,3,5-triazine(INCI: Bis-Ethylhexyloxyphenol Methoxyphenyl Triazin);2,4,6-tris-(biphenyl)-1,3,5-triazine;2,4-bis-(4′-di-neopentylamino-benzalmalonat)-6-(4″-butylaminobenzoat)-s-triazine,4-dicyanomethylen-2,6-dimethyl-1,4-dihydropyridin-N-(ethyloxysulfateester salt), titan dioxides, zink oxides, merocyanine, piperazinederivatives as mentioned in WO 2011/042088 without being limited tothese.

Possible solvents include but are not limited to: alcohols such asmethanol, ethanol, butanol, pentanol (amyl alcohol), ethylene glycol,propylene glycol, glycerol, butyl acetate, dimethlsulfoxide, acetone,methyl ethyl ketone, hydrocarbons such as hexane, pentane, oils such aszea mays oil, or the like.

The cosmetics may be solid, e.g. of a waxy appearance or the like, orliquid or in the form of pastes or creams, e.g. as emulsions, solutionsor suspensions, e.g. oil in water or water in oil (O/W or W/O) mixtures.They can thus form e.g. a solution, an emulsion of the water-in-oil(W/O) type or oil-in-water (O/W) type, or a multiple emulsion, forexample of the water-in-oil-in-water (W/O/W) type, a gel, ahydrodispersion, a solid stick or else an aerosol.

The possible surfactants include but are not limited to customary ones,e.g. anionic, non-ionic, amphoteric tensides, such as soaps or sodiumdodecylsulfate, or the substances disclosed in WO 2011/023582.

It is to be mentioned here that in view of their molecular structuresthe compounds of the formula I can also contribute surfactant propertiesto a composition according to the invention, so that this use is apreferred embodiment of the invention.

The composition comprising one or more compounds of the formula Iaccording to the invention can be applied to the skin or lips or otherbody surfaces, e.g. hair, nails or teeth, according to the use for whichit is intended. It can thus be used in a method for the cosmetictreatment of said body surfaces, e.g. the skin, comprising theapplication of the composition according to the invention to said bodysurface, e.g. the skin, for example for the purpose of toning it up, ofregenerating it or of smoothing out its e.g. wrinkles in skin and/or forcombating ageing, e.g. of the skin, or the damaging effects of UVradiation and/or for strengthening skin tissues, teeth, hair and/ornails against attacks from the surroundings.

In an alternative form, the composition according to the invention canbe used for the manufacture of a dermatological preparation.

Home Care Products

As possible home care products to be equipped with one or more of thecompounds of the formula I, among others, laundry detergents,dishwashing detergents, fabric softeners, hard surface cleaner or bleachcompositions; surface, laundry and/or dish cleaners, laundry soaps, airfresheners and odor eliminators, insect repellents, laundry detergents,fabric softeners, bleaching agents, organic cleaners, degreasers, stainremovers, window and glass cleaners, bathroom and toilet bowl cleaners,floor cleaners, carpet cleaners, pet odor removers, cat litterdeodorizers, car refresheners, furniture polishes, waterless handcleaners, disinfectants, spray deodorizers, food processing plantcleaners, coloring matters or other like home care applications may bementioned.

The home care products have customary compositions, For example, inaddition to surfactants, conventional solvents, dyes, preservatives,emulsifying agents, perfumes, antibacterial agents, thickeners,conditioners, antistatic agents, silicone surfactants, and other likeingredients that are typically present in conventional home careformulations may be comprised. Mixtures and/or combinations of theaforementioned additional formulating agents may also be employed in thepresent invention. The amounts of the additional formulating agents thatmay be employed in the present invention are within ranges that are wellknown to those skilled in the art and further formulating is performedusing processes that are also well known in the art.

Pharmaceuticals

Pharmaceuticals comprise one or more pharmaceutically active agents anda pharmaceutically acceptable carrier material.

Examples of such pharmaceuticals (pharmaceutical compositions) are e.g.solid (tablet, capsule, powder, medical chewing gum, lozenge,suppository) or liquid formulations (e.g. injection solution, infusionsolution, syrup, drinkable solution), a spray, or a pasty material, e.g.a gel or a cream.

Among the possible active ingredients, all drugs known in the art may beadded, e.g. (without that this enumeration is intended to be limiting)bronchodilators, antipyretics, analgetics, antiphlogistics,antiarrhythmics, blood-pressure reducing agents, vasodilators,anticholinergics, antiarteriosclerotics, enzymes, antibodies,secretolytics, ulcer preparations, antiproliferative agents,vasoconstrictors, expectorants, antitussiva, mucolytics, orsecretomotorics; in particular, free of antiallergics (including thosereferred to hereinbefore), such as α-sympathicometics (in particularPhenylephrin, Ephedrin, Tetryzolin, Naphazolin, Oxymetozolin,Xylometazolin or Tramazolin), antihistamines, non-steroidal or steroidalanti-inflammatory active substances (in particular Triamcinoloneacetonide, glucocorticoids, such as Prednisolone, Triamcinolonacetonide,Clomethasone, Dexamethasone, or Fluticasone), β₂ sympathomimetics; mastcell stabilizers, aromatase inhibitors; antiestrogens; topoisomerase Iinhibitors; topoisomerase II inhibitors; microtubule active compounds;alkylating compounds; histone deacetylase inhibitors; compounds whichinduce cell differentiation processes; cyclooxygenase inhibitors; MMPinhibittors; mTOR inhibitors; antineoplastic antimetabolites; platincompounds; compounds targeting/decreasing a protein or lipid kinaseactivity and further anti-angiogenic compounds; compounds which target,decrease or inhibit the activity of a protein or lipid phosphatase;gonadorelin agonists; anti-androgens; methionine aminopeptidaseinhibitors; bisphosphonates; biological response modifiers;antiproliferative antibodies; heparanase inhibitors; inhibitors of Rasoncogenic isoforms; telomerase inhibitors; proteasome inhibitors;compounds used in the treatment of hematologic malignancies; compoundswhich target, decrease or inhibit the activity of Flt-3; Hsp90inhibitors such as 17-AAG (17-allylamino-geldanamycin, NSC330507),17-DMAG (17-dimethylaminoethylamino-17-demethoxy-gelda-namycin,NSC707545), IPI-504, CNF1010, CNF2024, CNF1010 from ConformaTherapeutics; temozolomide (TEMODAL®); kinesin spindle proteininhibitors, such as SB715992 or SB743921 from GlaxoSmithKline, orpentamidine/chlorpromazine from CombinatoRx; MEK inhibitors such asARRY142886 from Array PioPharma, AZD6244 from AstraZeneca, PD181461 fromPfizer, leucovorin, EDG binders, antileukemia compounds, ribonucleotidereductase inhibitors, S-adenosylmethionine decarboxylase inhibitors,antiproliferative anti-bodies or other chemotherapeutic compounds;tricyclics, e.g. benzodiazepines including mitochondrialbenzodiazepine-ligands MAO inhibitors, SSRI's, SNRI's, NK receptorantagonists, CRF-receptor antagonists, 5HT7 receptor-antagonists, mGlureceptor agonists/antagonist/modulators, GABA-A or GABA-A/B receptoragonist/antagonists or modulators, vasopressin receptor antagonists,herbal medicine such as St. John's Wort, 5-HT1A receptor agonists,vasopressin receptor-antagonists, acetylcholine-esterase inhibitors,such as rivastigmine or donepezil, mixed acetylcholine/butyrylcholineesterase-inhibitors. nicotinic-alpha7-receptor agonists, typical oratypical antipsychotics, such as clozapine or haloperidol,nicotinic-alpha7-receptor agonists, antimanic agents (e.g. lithium,Carbamazepine, Valproate) or any atypical or typical antipsychotic; orthe like; pharmaceutically acceptable salts thereof, if salt-forminggroups are present; or combinations of two or more of the aforementionedactive substances or their pharmaceutically acceptable salts.

Pharmaceutical compositions comprising one or more active ingredientsand one or more compounds of the formula I in association with at leastone pharmaceutical acceptable carrier or diluent may be manufactured inconventional manner by mixing with a pharmaceutically acceptable carrieror diluent.

The invention relates also to pharmaceutical compositions comprising anantimicrobially effective amount, especially an amount effective in thetreatment of one of the above-mentioned disorders, of one or morecompounds of the formula I, a pharmaceutically acceptable salt thereof,and/or an ester thereof, together with one or more pharmaceuticallyacceptable carriers that are suitable for topical, enteral, for exampleoral or rectal, or parenteral administration and that may be inorganicor organic, solid or liquid. There can be used for oral administrationespecially tablets or gelatin capsules that comprise the activeingredient together with diluents, for example lactose, dextrose,mannitol, and/or glycerol, and/or lubricants and/or polyethylene glycol.Tablets may also comprise binders, for example magnesium aluminumsilicate, starches, such as corn, wheat or rice starch, gelatin,methylcellulose, sodium carboxymethylcellulose and/orpolyvinylpyrrolidone, and, if desired, disintegrators, for examplestarches, agar, alginic acid or a salt thereof, such as sodium alginate,and/or effervescent mixtures, or adsorbents, dyes, flavorings andsweeteners. It is also possible to use the pharmacologically activecompounds of the present invention in the form of parenterallyadministrable compositions or in the form of infusion solutions. Thepharmaceutical compositions may be sterilized and/or may compriseexcipients, for example preservatives, stabilizers, wetting compoundsand/or emulsifiers, solubilizers, salts for regulating the osmoticpressure and/or buffers. The present pharmaceutical compositions, whichmay, if desired, comprise other pharmacologically active substances areprepared in a manner known per se, for example by means of conventionalmixing, granulating, confectioning, dissolving or lyophilizingprocesses, and comprise approximately from 1% to 99% by weight,especially from approximately 1% to approximately 60%, activeingredient(s) and 0.001 to 10, 0.01 to 8, 0.02 to 6 or 0.03 to 5 weightpercent of the compound(s) of the formula I, a pharmaceuticallyacceptable salt thereof and/or an ester thereof. Also the use of theirpreservative or antimicrobial properties in said pharmaceuticalcompositions by the addition of one or more compounds of the formula Iis included.

Additives, both in the case of foods and of cosmetics, as well as in thecase of pharmaceuticals (the term pharmaceuticals also includingnutraceuticals), may exhibit more than one property as selected from theabove lists or other not cited properties, e.g. preservatives may alsoact as acidity regulators and vice versa, or e.g. antioxidants may actas preservatives as well as acidity regulators, or other thinkable multifunctional uses.

Medical Devices

Medical devices are especially devices intended for use in the diagnosisof disease or other conditions, or in the cure, mitigation, treatment,or prevention of disease, in man or other animals, and mean e.g. anyinstrument, apparatus, appliance, material or other article, whetherused alone or in combination, including the software necessary for itsproper application intended by the manufacturer to be used for humanbeings for the purpose of:

-   -   diagnosis, prevention, monitoring, treatment or alleviation of        disease,    -   diagnosis, monitoring, treatment, alleviation of or compensation        for an injury or handicap,    -   investigation, replacement or modification of the anatomy or of        a physiological process,    -   control of conception,        and which does not achieve its principal intended action in or        on the human body by pharmacological, immunological or metabolic        means, but which may be assisted in its function by such means.

Among the medical devices, among others, e.g. implants, prosthesis,plasters (=adhesive tapes), (wound) dressing materials, bandages, cottonwool, gauze bandages, surgical instruments, tooth brushes, syringes,syringe needles, medication containers, infusion bottles, infusiontubes, valves or multiports used in infusion, infusion needles, infusionassemblies, surgical instruments, catheters, artificial or naturaltissues or membranes, tooth brushes, and the like may be mentioned.

Possible implants include but are not limited to:

a) Surgical meshes or other 2-dimensionally extended or extendablematerials (such as membranes), such as polypropylene meshes (e.g. BARDMESH® from Bard Inc., SURGIPRO® from US Surgical, Inc., TRELEX® fromBoston Scientific, PROLENE® or MERSILENE® from Ethicon, Inc.), polyestermeshes (e.g. MERSILENE® from Ethicon), expanded polytetrafluoroethylenmeshes (e.g. SOFT TISSUE PATCH® from W.L. Gore & Associates, Inc),polyamide materials or the like, e.g. for the repair of hernias; or suchmeshes or materials 2-dimensionally extended or extendable materials,such as polyglactin (e.g.VICRYL® from Ethicon, Inc.), polyglykolate(e.g. DEXON® from US Surgical, Inc.), polydioxanone (PDS), polyglyconate(e.g. MAXON®, Davis & Geck, Gosport, UK) or collagene materials, e.g.COOK SURGISIS® from Cook Biomedical, Inc.; other possible membrane ormesh materials include FLUORO-TEX® Pericardial and Peritoneum SurgicalMembrane or FLUORO-TEX Dura Substitute (each from C.R. Bard) orrPRECLUDE® Pericardial Membrane PRECLUDE® Peritoneal Membrane andPRECLUDE® Dura Substitute Membrane each from W.L. Gore & Associates,silicone elastomers, such as SILASTIC Rx® Medical Grade Sheeting fromDow Corning or mikroporous Polypropylen from Celgard, Inc., for examplewhere the implant is used to seal compartmenting tissues or structuresin the body, such as peritoneum, pleura, diaphragma, lung, pericard orthe like;b) electrode coatings, e.g. for electrodes of pacemakers or neural ormuscular stimulation or the like, e.g. made from tungsten, silicon,platinum-iridium or stainless steel or combinations thereof;c) degradable or non-degradable bone or cartilage implants;d) orthopaedic implants, such as hard tissue, bone or joint replacingimplants, for example for hip or knee or other joint repair, e.g.implants made from stainless steel, cobalt-chromium alloys, titanium ortitanium alloys, pure titanium, tantalum, plastics materials such aspolyethylene, polypropylene, polylactate, carbon fibre, ceramics orcompounds of two or more such materials;e) screws, nails, threads, plates or other hard fixation materials forhard tissues, e.g. from the materials mentioned under d);f) oral, such as dental implants, e.g. from the materials mentionedunder d);g) Bone fillers, such as bone cement composites, hydroxyl apatitecomposites or polycaprolactone (Blurr plug);h) implants coming into contact with blood, such as vascular grafts,e.g. from biocompatible plastics materials, such as extendedpolytetrafluoroethylene or poly[ethylene terephthalate], stents (e.g.from metals or metal alloys, such as (e.g. 316L) stainless steel,cobalt-chromium-nickel-molybdenum-iron alloy, Tantalum, shape memoryalloys, e.g. nitinol, or (e.g. shape memory) polymer materials, such aspolyethylene or polyurethane), heart or venous valves (e.g. from polymeror metal or natural materials or combinations thereof, e.g. pyrolyticcarbon, titanium coated with pyrolytic carbon, and the sewing ring cuffis e.g. teflon, polyester or dacron), stent/valve combinations, orcontinuous accesses e.g. to veins, or to the peritoneum e.g. forperitoneal dialysis or the like;i) implants for delivery of signals or chemical substances, e.g. drugs,coming into contact with tissue and/or body fluids, e.g. pumps fordelivery of drugs or pacemakers;j) organs or tissues for transplantation (e.g. to decrease theexpression of antigens evoking transplant rejection), especiallyautografts, allografts, heterografts or xenografts;k) skin substitutes or wound coating materials, such as natural (e.g.keratinocytes in combination with human fibroblasts in bovine type Icollagen or other ECM proteins and cytokines, such as Apligraf®(Organogenisis Inc.), or from synthetics, or combinations with naturalmaterials e.g. synthetic polysiloxanes with bovine type I collagen andchondroitin-6-sulphate (e.g. Integra® (Johnson & Johnson Medica CareLife)) or preferably from synthetics alone or combined with human dermaltissue (e.g. Tanscyte® (Advanced Tissue Sciences Inc.)), allografts,collagen (e.g. in reconstituted form) or the like;l) suturing materials (especially for internal sutures not accessiblefrom the outside), e.g. from absorbable or non-absorbable synthetics ornatural materials (e.g. cat gut).

Especially preferred are artificial implants made from metals, metalalloys, synthetic materials (=polymers) (either degradable ornon-degradable), carbon fibres, boranes, ceramics, glass or bonereplacement materials, especially of the types a) to i) or k) to l)mentioned above, including composites of two or more such materials.

The implants may be for permanent (e.g. in the case of jointreplacement) or transitory (e.g. in the case of fixing devices or skinreplacements) insertion or other administration.

Especially here the biofilm inhibiting usefulness of the compound(s) offormula I and of compositions comprising them is of advantage.

Active Packaging Materials

Among the active packaging materials, e.g. food or beverage orpharmaceutical or surgical packaging material having a spoilagepreventing/preservative effect e.g. against colonialisation by bacterialor other microorganismic films or against spoiling of materials cominginto contact with other perishable products can be mentioned, e.g. cans,wraps, foils, bottles, mugs, cartons, tubs, bags, cartridges, tubes,sachets, ampoules, sacks, or the like.

Both with regard to medical devices and to active packaging materials,as well as with regard to personal care products used having apredetermined shape, the application of compound(s) of the formula I isespecially by coating e.g. on surfaces coming into contact withperishable products or a human or an animal, or bulk integration (e.g.by mixing of starting materials and/or impregnation of final products)into the material.

The compound(s) of the formula I to medical devices and active packagingmaterials can especially be applied (alone or in combination withappropriate carrier materials) on surfaces coming into contact withperishable products or a human or an animal, e.g. in the form of acoating, or applied by bulk integration into the material.

The materials equipped (which form an embodiment of the invention) or tobe equipped with one or more compounds of the formula I may comprise thecompound(s) of the formula I, a physiologically acceptable salt thereofand/or an ester thereof, either in admixture to the bulk of thematerial, or (in the case of products with a stable surface) by covalentand/or non-covalent attachment to (parts or the whole of) said surface.

For covalent attachment, the surface must either expose or be chemicallymodified to expose functional groups which would allow for covalentbonding of the compound of the formula I either directly or via a spacermolecule.

In the case of the covalently bound (at least bivalent) linkermolecules, these may allow covalent or non-covalent binding of thecompounds of the formula I.

The linker in the covalent attachment method can be any linker.

Covalent binding of the compounds of the formula I with or withoutlinkers can take place directly by reacting their precursors with thesurfaces without activation or to activated surfaces on the implants orother products. Examples are

1. epoxy- or activated ester-functionalized surfaces, where reactionwith OH— or amino groups in the linker precursors is possible.2. Where the linker precursors are organic compounds which are furnishedterminally with a thiol group, they can be bound e.g. via gold-platedsurfaces or maleinimide-layered surfaces.3.) Linker precursors which, during the process of manufacture, arefurnished terminally with a carboxyl or phosphate group, can beactivated to active esters or the like, e.g. with EDC, so that an OH—,SH— or amino-reactive on the surface can be bound.4.) Precursors for homo- or preferably hetero-bifunctional cross-linkerwhich can be bound to reactive groups at the surface, such as carboxyl,epoxy, OH, SH, aldehyde or amino groups; or other known methods.5.) Other directly functionalized surfaces, e.g. especially polymerswith plasma-coated aldehydes.

Other possible activations for both covalent and non-covalent bindinginclude but are not limited to glow-discharged surfaces, electrosticallycharged surfaces, and/or roughened surfaces. Also coating withmaterials, e.g. gels, varnishes, paints or the like, comprising thecompound(s) of the formula I, is a method for providing their surfaceswith these compounds.

In the (preferred) case of the non-covalent attachment, the material canbe any substrate. This substrate could be a synthetic polymer (i.e.polyacrylate, polylactide-co-glycolide, polyethylene, or polypropylene),carbon fibre, glass, boranes, metal (i.e. titanium or stainless steel),natural polymer (i.e. collagen or alginate), or any other surface thatis capable of supporting a coating, e.g. in solid or fibre form,respectively. Composites of two or more such materials are alsoincluded. The non-covalent can, for example, be via adsorption,integration into a coating matrix or the like.

The compounds of the formula I in the embodiments of the invention, in afurther embodiment, can be used also where the materials (products) withwhich they are associated (e.g. by mixing in) require a heat treatment,e.g. to achieve pasteurization sterilization or the like.

Thus, in one embodiment, the one or more compounds of the formula Iis/are heat stable. In one example the compound(s) of the formula Ifully or partially retain(s) structure and activity e.g. regarding itspreservative properties after heating. Heating of the antimicrobialcomposition can be performed at 60-130° C., such as in the range of60-65° C., 65-70° C., 70-75° C., 75-80° C., 80-85° C., 85-90° C., 90-95°C., 95-100° C., 100-105° C., 105-110° C., 110-115° C., 115-120° C.,120-125° C., 125-130° C.

In one embodiment heating is performed at about 65-75° C., morepreferred at about 70° C. In one embodiment heating is performed atabout 90-110° C., more preferred at about 100° C.

In yet another embodiment heating is performed at about 120-125° C.,more preferred at about 121° C.

According to the present invention, heating can be performed for shorteror longer periods of time, such as from a minute to several hours.Heating can for example be performed for a few minutes such as in therange of about 1-5 minutes, 5-10 minutes, 10-15 minutes, 15-20 minutes,20-25 minutes, 25-30 minutes, 30 minutes-to 1 hour.

For the purpose of the invention other known preserving agents or knownpreservatives may be added to the pharmaceutical incl. nutraceutical andcosmeceutical, nutritive or cosmetic product as well as to thecomposition.

Preferred combinations of the compounds of the invention for use in foodand beverages are with weak organic acids, especially preferred arecombinations with sorbic acid and/or benzoic acid and their appropriatesalts, or with natural preservatives.

Among possible preferred combinations of the compounds of the inventionfor cosmetic use are combinations with C₁-C₄ alkyl para-hydroxybenzoateor its salts, e.g. methylparaben, ethylparaben, propylparaben,isopropylparaben, butylparaben, isobutylparaben and their appropriatesalts, benzylparaben, benzoic acid or its salts, e.g. sodium benzoate,N-(3-chloroallyl)hexaminium chloride, alcohols or polyols, such asethanol, propylene glycol, benzyl alcohol or 2-phenoxyethanol,benzalkonium chloride, chloroacetamide, thimerosal, benzalkoniumchloride, cetylpyridinium chloride, N-(3-chloroallyl)hexaminiumchloride, formaldehyde donors, such as imidazolidinyl urea, diazolidinylurea, or DMDM hydantoin, isothiazolinones, such as KATHON® CG, availablecommercially from Rohm & Haas, Philadelphia, Pa., which contains achloro-substituted isothiazolinone (methylchloroisothiazolinone), otherchlorinated aromatic compounds, such as chlorphenesin, phenoxyethanol,vicinal diols, such as a 1,2-alkane diol or a glyceryl monoether, suchas glyceryl laurate, decyl glycoside isothiazolinone compounds, such asmethylisothiazolinone, e.g. 2-methyl-3(2H)isothiazolinone, propionicacid and its salts, undec-10-enoic acid and salts, Scutellariabaicalensis extracts (such as e.g. available from BMB-FS, or the like),or mixtures of two or more such preservatives.

In all materials, the compound(s) of the formula I can also be used asemulsifiers, in addition to use of their preservative properties.

The compound or compounds of the formula I are preferably comprised,taking the weight or the material to which it is added and thecompound(s) of formula I as 100 weight %, in a relative weight share of0.00001 to 10 weight percent.

In the foods or beverages according to the invention, the compound orcompounds of the formula I are preferably added/comprised in aconcentration e.g. in the range from 50 to 20000 ppm, e.g. from 100 to1000 ppm, for example from 10 to 120 ppm, such as from 30 to 60 ppm, ore.g. from 0.1-150 ppm, where ppm refers to weight parts per million.

“Minimal inhibitory concentration” (MIC) is a term for which no standardtime period is routinely defined or understood. In the medical fields,MIC is frequently employed to designate the concentration of a substancewhich prohibits the growth of a single type of microorganism inover-night incubation as compared to a positive control without thesubstance. However, the rest of the scientific community has adopted theterm MIC to mean any of a number of conditions of period of incubationand degree of inhibition.

Even within the medical field, it is recognized that an MIC valuedeveloped over a period of 24 hours incubation may not be the same valuedeveloped after 48 hours or longer. In other words, a substance mayexhibit an observable MIC during the first 24 hours of an experiment,but exhibit no measurable MIC relative to the positive control after 48hours.

The following table gives some of the compounds of the formula I thatare of interest in the various embodiments of the present invention.

TABLE 1 Name Cpd. (if known: CAS Num number): ber 2,17,18- trihydroxy-hexacosanoic acid 22-O- [6-isovaleroyl- hexapyranosyl- (1→2)-5-acetyl-pentapyranosyl- (1→2)-penta- pytanosid]- [1]

[2]

Glykenin-IIC 134528-36-2 [3]

[4]

[5]

Glykenin IIIB or Glykenin IIIC 134528-37-3, 134479-71-3 [6]

Glykenin IVC or IVB 134479-72-4, 134528-38-4 [7]

[8]

[9]

[11]

[12]

[13]

[14]

Glykenin DGC or Glykenin DGB 112965-51-2, 112848-53-0 [16]

[17]

Antibiotic F 19848A 895129-04-1 [10]

[18]

[19]

[20]

[21]

The preserving properties of the compounds of the invention e.g.compounds of the formula I can be evaluated according methods cited inthe art such as WO 2010/062548. For example, they can be determined forbeverages using the method described in Example 3 in WO 2010/062548which is incorporated herein by reference. For example, a singlepreparation of base beverage is employed to prepare each of five testsand consists of 4% apple juice, 68 g/l sucrose, 52 g/l glucose, 2 g/lfructose in batch water which is formulated to 90 ppm hardness withclalcium chloride and magnesium chloride. A pH of 3.4 is achievedthrough combinations of malic acid and sodium malate for allpreparations regardless of the presence or absence of compounds of theformula I. The total combined quantity of sodium malate and malic acidis near constant, but the ratio of malic acid and malate may varyslightly given the presence of compound of the formula I. It is relevantthat the beverage employed for testing does not naturally contain anysubstance with measurable antimicrobial activity such as in essentialoils. Where required, compound of the formula I is supplemented fromseparately prepared stock solutions. Dimethyl dicarbonate is deliveredby means of a hypodermic needle (Hamilton syringe) through septum thatseals the test vessel against loss of moisture. Dimethyl dicarbonatestock solution consists of 1 ml dimethyl dicarbonate (1.25 g) in 49 mlof 100% ethanol (25 mg/ml). Hence, a microliter of stock contains 25microgram of dimethyl dicarbonate. Each of the five tests employs thesame bio-indicator organisms; Growth (+) versus no growth (−) isestablished by visual inspection or spectrophotometrically (see e.g.Examples below). The organism names and their strain numbers, as well asincubation times and details on deviating assay conditions, if any wereused, are mentioned in the Examples.

Among the preferred embodiments of the invention, the following are tobe mentioned:

A) The first embodiment of the invention is that defined in claim 1, ora method comprising the use mentioned therein.B) Especially preferred is said use or method, where the material towhich the agent is added is a cosmetic, a food or a beverage.C) Another invention embodiment related to the use or method accordingto paragraph A) or B), where in the compound of the formula I m is 3 to5, n is 2 to 5, o is 0 or 1, p is 5 to 15 and R is a moiety of thesubformula

wherein the rings A, B and C are monosaccharide moieties eachindependently from the others with 5 or 6 ring members, wherein one ormore of the hydroxyl groups may be acylated, preferably by aC₂-C₁₀alkanoic, more preferably a C₃-C₁₀alkanoic acid.D) Another invention embodiment relates to the use or method accordingto paragraph A) above, wherein the compound or mixture of compounds ofthe formula I comprises, preferably, at least one compound selected fromthe group of compounds mentioned in table 1, or a physiologicallyacceptable salt thereof.E) Another invention embodiment relates to the use or method accordingto any one of paragraphs A) to D) above, wherein the compound orcompounds of the formula I, or a physiologically acceptable salt, or aphysiologically acceptable ester thereof, is added to enhance thestability against microorganisms.F) Another invention embodiment relates to the use or method accordingto paragraph E) above, where the microorganism is at least onemicroorganism selected from the group consisting of mold, yeast andbacteria of a beverage or a food or a cosmetic.G) Another invention embodiment relates to the use or method accordingto any one of paragraphs A) to F) above, where at least one additionalpreservative is added.H) Another invention embodiment relates to the use or method accordingto any one of paragraphs A) to G) above, where the compound or compoundsof the formula I, a physiologically acceptable salt thereof, and/or anester thereof, is added in the form of an extract (this term including aprecipitate) from a natural source or obtained from such an extract.I) Another invention embodiment relates to the use or method accordingto paragraph H), where the source of the extract is a Dacryopinax, aDitiola and/or a Femsjonia fungus.J) Another invention embodiment relates to the use or method accordingto paragraph H), where the source of the extract is Dacryopinaxspathularia, Dacrymyces sp., Ditiola radicata, Ditiola nuda and/orFemsjonia luteo-alba (=Ditiola pezizaeformis).K) Another invention embodiment relates to the use or method accordingto paragraph J) above, where the source of the extract is Dacryopinaxspathularia strain FU50088, Ditiola radicata strain MUCL 53180, Ditiolanuda strain CBS 173.60 or Femsjonia luteo-alba (=Ditiola pezizaeformis)strain MUCL 53500.L) Another invention embodiment relates to the use or method accordingto any one of paragraphs A) to K), where the material is subjected to aheat treatment before, during or after addition of the compound(s) ofthe formula I, a physiologically acceptable salt thereof and/or an esterthereof, as defined in any one of paragraphs A), C), D) or H) to K),especially heating the material to a temperature from 60 to 130° C.M) Another invention embodiment relates to a compound or a mixture ofcompounds of the formula I shown in paragraph A) or as defined in anyone of paragraphs C), D) or H) to L), where the moiety R carries atleast one hydroxyl group esterified with an acid with 3 or more carbonatoms, a physiologically acceptable salt, and/or an ester thereof.N) Another invention embodiment relates to the compound or compoundmixture of paragraph M), wherein the acid is a C₃-C₁₀-alkanoic acid,especially isovaleric acid; a physiologically acceptable salt, and/or anester thereof.O) Another invention embodiment relates to a compound of the formula Ishown in claim 1, selected from the group of compounds represented inTable 1 with the following compound numbers: [1], [12], [13], [14], [17]and [18], and in a broader aspect from compound [4], a physiologicallyacceptable salt, and/or an ester thereof.P) A further embodiment of the invention relates to a preservative orantimicrobial composition, comprising as active agent a compound or amixture of compounds of the formula I, a physiologically acceptable saltthereof, and/or an ester thereof, as shown or defined in any one ofparagraphs A), C), D) and H) to O), alone or with another additive, suchas a carrier material, where the preservative composition is especiallyfor use in a cosmetic, a food, a beverage, a pharmaceutical, a medicaldevice, or an active packaging material.Q) Another invention embodiment relates to the composition according toparagraph P) which is a powder.R) Another invention embodiment relates to the composition according toparagraph P) which is a liquid.S) Yet another invention embodiment relates to the composition accordingto paragraph P) which is a coating or film.T) Another invention embodiment relates to the composition according toany one of paragraphs P) to S), wherein the preservative orantimicrobial composition is for enhancing the stability againstmicroorganisms.U) Another invention embodiment relates to the composition according toparagraph T), wherein the microorganisms are at least one microorganismselected from the group consisting of mold, yeast and bacteria.V) Another invention embodiment relates to the composition according toany one of paragraphs P) to U), being a preservative or antimicrobialcomposition for a pharmaceutical, a medical device, a food container, abeverage container, or especially a food, a beverage or a cosmetic or ahome care product.W) Another invention embodiment relates to the composition according toany one of paragraphs P) to V), which comprises an additionalpreservative.Y) Another invention embodiment relates to the composition according toany one of paragraphs P) to W), which is a precursor of a beverage,especially a concentrate, a syrup or a powder.Z) Another invention embodiment relates to an extract comprising one ormore compounds of the formula I, a physiologically acceptable saltthereof, and/or an ester thereof, as shown or defined in any one ofparagraphs A), C), D) or H) to O).AA) Another invention embodiment relates to a method of enhancingmicrobial stability of a material, comprising adding one or morecompounds of the formula I, a physiologically acceptable salt thereof,and/or an ester thereof, as shown or defined in any one of paragraphsA), C), D) or H) to O) to a material, preferably a material selectedfrom the group consisting of a cosmetic, a food, a beverage, apharmaceutical, a medical device, and an active packaging material.BA) Another invention embodiment relates to the method of paragraph AA),wherein the material is a beverage or a food.CA) Another invention embodiment relates to the method of paragraph AA),wherein the material is a cosmetic.DA) Another invention embodiment relates to a material comprising, as orwithin a coating and/or as admixture, an additive in the form of acompound or a mixture of compounds of the formula I, a physiologicallyacceptable salt thereof and/or an ester thereof, as defined in any oneof paragraphs A), C), D) or H) to O).EA) Another invention embodiment relates to the material of paragraphDA), which is a cosmetic, a food, a beverage, a pharmaceutical, amedical device, or an active packaging material.FA) Another invention embodiment relates to the material according toparagraph DA) which is a beverage.GA) Another invention embodiment relates to the material in the form ofa compound or a mixture of compounds of the formula I, a physiologicallyacceptable salt thereof and/or an ester thereof, according to paragraphFA), where the beverage is selected from the group consisting of water,flavoured water, fortified water, a flavoured beverage, carbonatedwater, a juice, cola, lemon-lime, ginger ale, root beer beverages whichare carbonated in the manner of soft drinks, a syrup, a diet beverages,a carbonated soft drink, a fruit juice, other fruit containing beverageswhich provide the flavor of fruit juices and contain greater than 0%fruit juice but less than 100% fruit juice, fruit flavored beverages,vegetable juices, vegetable containing beverages, which provide theflavor of any of the aforementioned vegetable juices and contain greaterthan 0% vegetable juice but less than 100% vegetable juice, isotonicbeverages, non-isotonic beverages, soft drinks containing a fruit juice,coffee, tea, tea beverages prepared from tea concentrate, extracts, orpowders, drinkable dairy products, hot chocolate, chocolatepowders/mixes, drinkable soy products, non-diary milks, alcoholicbeverages, fruit smoothies, horchata, sport drinks, energy drinks,health drinks, wellness drinks, shakes, protein drinks, drinkable soyyogurts, low acid beverages, acidified beverages, nectars, tonics,frozen carbonated beverages, frozen uncarbonated beverages, liquid mealreplacements, infant formulations, and combinations or mixtures thereof.HA) Another invention embodiment relates to the material according toparagraph DA) which is a beverage precursor, especially a concentrate,syrup or powder.IA) Another invention embodiment relates to the material according toparagraph DA) which is a food.JA) Another invention embodiment relates to the material according toparagraph DA) which is a cosmetic.KA) Another invention embodiment relates to the material in the form ofa cosmetic according to paragraph JA) which is cream, emulsion, lotion,gel or oil for the skin; a face masks, a tinted base, a make-up powder,an after-bath powder, a hygienic powder, a toilet soap, a deodorantsoap, a perfumes, a toilet water, an eau de Cologne, a bath or showerpreparation; a depilatory; a deodorant, an anti-perspirant, a hair careproduct; a setting product; a cleansing product; a conditioning product;a hairdressing product; a shaving products; a product for making up andremoving make-up from the face and the eyes, a product intended forapplication to the lips, a products for care of the teeth and/or themouth; a product for nail care and/or make-up, a product for externalintimate hygiene, a sunbathing product, a product for tanning withoutsun, a skin-whitening product, an anti-wrinkle product, a tampon, asanitary towel, a diaper or a handkerchief.LA) Another invention embodiment relates to the cosmetic materialaccording to any one of paragraphs JA) and LA), which comprises one ormore additives selected from the group consisting of abrasives,absorbents, anti-cakings, anti-corrosives, anti-dandruffs,anti-foamings, anti-microbials, anti-oxidants, anti-perspirants,anti-plaques, anti-seborrhoeics, anti-statics, astringents, bindings,bleachings, bufferings, bulkings, chelatings, cleansings, cosmeticcolorants, denaturants, deodorants, depilatories, detanglings,emollients, emulsifiers, emulsion stabilizers, film formings, foamings,foam boosters, gel formers, hair conditioners, hair dyes, hair fixers,hair waving or straighteners, humectants, hydrotropers, keratolytics,masking agents, moisturing, nail conditioners, opacifiers, oral care,oxidizers, pearlescents, plasticizers, preservatives, propellants, skinprotectors, smoothers, solvents, soothers, stabilizers, surfactants,tanning, tonics, UV absorbers, UV filters, and viscosity controllers.MA) Another invention embodiment relates to the cosmetic materialaccording to any one of paragraphs JA) and LA), where the formulationscan be or comprise or contain cosmetic additives selected fromsunscreens, preservatives, bactericides, fungicides, virucides, coolingsubstances, insect repellents, plant extracts, antiinflammatorysubstances, wound healing accelerators, film-forming substances,customary antioxidants, vitamins, 2-hydroxycarboxylic acids, skincolorants, active ingredients for promoting hair growth, skin careproducts, softening, moisturizing and/or moisture-retaining substances,fats, oils, saturated fatty acids, monounsaturated or polyunsaturatedfatty acids, alfa-hydroxy acids, polyhydroxy fatty acids or theirderivatives, waxes, alcohols, polyols, polymers, foam stabilizers,electrolytes, organic solvents, silicone derivatives or chelatingagents, antidandruff substances, hair care products, perfumes,antifoams, dyestuffs, pigments with a coloring action, thickeners,surface-active substances, emulsifiers, plant parts and plant extracts,animal extracts, proteins, protein hydrolysates, yeast extracts, hop andwheat extracts, peptides and thymus extracts.NA) Another invention embodiment relates to the material according toany one of paragraphs DA) to MA) comprising an additional preservative.PA) Another invention embodiment relates to the material according toany one of paragraphs DA) to NA) which is obtained after heat treatment,especially at 60 to 130° C.QA) Another invention embodiment relates to a compound of the formula Ior a mixture of such compounds, according to any one of paragraphs A),B) and H) to O) or a composition comprising them, especially accordingto any one of paragraphs P) to S) mentioned above, as a biofilminhibiting agent and its corresponding use, e.g. by administering, or inmethods comprising administering, one or more compounds of the formulaI, or a composition comprising them, to surfaces or materials cominginto contact with surfaces.

In a preferred embodiment, the invention relates to (the use of) one ormore compounds of the above formula I, one or more physiologicallyacceptable salts of a compound of the above formula I, or a mixturethereof,

as agent with preservative properties against (i) Gram-positive bacteriaand/or (ii) fungi, wherein the

-   (i) Gram-positive bacteria are selected from the group consisting of    the genera Bacillus, Brevibacterium, Lactobacillus, Micrococcus,    Staphylococcus, Streptococcus, Clostridium, Chlamydia, Enterococcus,    Listeria, Corynebacterium, Leuconostoc, Pediococcus,    Propionibacterium,    and the fungi preferably are selected from the group consisting of-   (ii-a) fungi from the families Trichocomaceae, Arthrodermataceae and    Mucoraceae, more preferably molds (moulds) of the genera    Aspergillus, Botryotinia, Byssochlamys, Magnaporthe, Paecilomyces,    Neosartorya, Mucor, Penicillium, Rhizopus, Talaromyces, and    Trichophyton,-   (ii-b) yeasts from the order Saccharomycetales, preferably yeasts    from the families Saccharomycetaceae or Pichiaceae, more preferably    from the group consisting of the genera Brettanomyces, Candida,    Dekkera, Pichia, Saccharomyces, and Zygosaccharomyces,    preferably comprising adding the agent to a material, where said    material is selected from the group consisting of a cosmetic    product, a food product, a beverage, a pharmaceutical product, a    medical device, a medical hygiene product, a home care product, and    an active packaging material.

In a more preferred embodiment, the invention relates to (the use of)one or more compounds of the above formula I, one or morephysiologically acceptable salts of a compound of the above formula I,or a mixture thereof,

wherein m is 3 to 5, n is 3, o is 0 or 1 and p is 11 to 14, preferably mis 3 to 5, n is 3, o is 0 or 1 and p is 12 or 13,andR is a trisaccharide carbohydrate moiety of the subformula

bound via a carbon atom to the binding oxygen (via the bond indicated bythe dotted line), wherein ring A is a xylopyranoside moiety, ring B is axylopyranosyl moiety, and ring C is glucopyranosyl moiety, and whereinone or more of the hydroxyl groups of said rings are esterified with aC₂-C₁₀-alkanoic acid, preferably a C₃-C₁₀-alkanoic acid, more preferablya C₃-C₆-alkanoic acid,as agent with preservative properties against (i) Gram-positive bacteriaand/or (ii) fungi, as indicated above, preferably comprising adding theagent to a material, where said material is preferably selected from thegroup consisting of a cosmetic product, a food product, a beverage, apharmaceutical product, a medical device, a medical hygiene product, ahome care product, and an active packaging material.

As already mentioned, and especially due to their excellent andgenerally superior antimicrobial properties (in particular regardingyeasts and molds), preferred compounds or mixtures of compounds of theformula I shown above are defined by a trisaccharide carbohydrate moietyR carrying at least one hydroxyl group esterified with an acid with 3 ormore carbon atoms, particularly wherein the acid is a C₃-C₁₀-alkanoicacid, especially wherein the acid is a C₃-C₆-alkanoic acid, and/or aphysiologically acceptable salt thereof.

In a particularly preferred embodiment, the invention relates to (theuse of) one or more compounds of the above formula I, one or morephysiologically acceptable salts of a compound of the above formula I,or a mixture thereof (preferably as defined in one of the preferred orparticularly preferred embodiments herein) as agent with preservativeproperties against

-   -   bacteria selected from the group consisting of Bacillus        subtilis, Bacillus cereus, Brevibacterium epidermidis,        Brevibacterium linens, Chlamydia trachomatis, Clostridium        perfringens, Clostridium botulinum, Clostridium sporogenes,        Corynebacterium xerosis, Corynebacterium variabile,        Corynebacterium minutissimum, Enterococcus faecalis,        Lactobacillus plantarum, Listeria monocytogenes, Listeria        welshimeri, Micrococcus luteus, Propionibacterium acnes,        Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus        mutans, and Streptococcus pneumoniae,        and/or    -   filamentous fungi selected from the group consisting of        Aspergillus brasiliensis, Aspergillus flavus, Aspergillus        fumigatus, Aspergillus niger, Botrytis cinerea, Byssochlamys        fulva, Magnaporthe grisea (Magnaporthe oryzae, Pyricularia        oryzae), Mucor plumbeus, Rhizopus arrhizus, Rhizopus nigricans,        Rhizopus stolonifer, and Talaromyces luteus,        and/or    -   yeast selected from the group consisting of Brettanomyces        bruxellensis, Brettanomyces naardenensis, Candida albicans,        Candida glabrata, Candida lusitaniae, Candida tropicalis,        Dekkera bruxellensis, Dekkera naardenensis, Saccharomyces        cerevisiae, Zygosaccharomyces bailiff, Zygosaccharomyces        bisporus, Zygosaccharomyces florentinus, and Zygosaccharomyces        rouxii.

Within the scope of the present text, the terms “for oral consumption”,“orally consumable” or “food product” and the like in particular referto materials which are intended to be swallowed by a human being in anunchanged (i.e. by direct oral consumption, “ready-to-eat”,“ready-to-drink”) or processed state and then to be digested.

The term “ready-to-use” product refers to a product, the composition ofwhich, in terms of the substances which determine the flavour, is(essentially) complete. The term “ready-to-use” product includescarbonated and non-carbonated liquids and viscous or semisolid products.Examples of “ready-to-use” products include deep-frozen products which,prior to consumption, are be defrosted and heated before consumption.The ready-to-use products may also be “ready-to-eat” or“ready-to-drink”, like e.g. carbonated beverages, flavoured milk,(water) ice, yoghurts, and the like, or may have to be diluted withwater before oral consumption, which is for example the case forbeverage syrups.

Yeasts are able to grow in orally consumable compositions, such as foodsand beverages, with a low pH values (generally pH 5.0 or lower), and inthe presence of sugars, organic acids or other easily metabolized carbonsources. During their growth, yeasts metabolize some food components andproduce metabolic products. This causes the physical, chemical, andsensory properties of an orally consumable composition to change, andthe composition is spoiled. The growth of yeast within orally consumablecompositions is often seen on their surface, as in cheeses or meats, orby the fermentation of sugars in beverages, such as juices, andsemi-liquid products, such as syrups and jams.

Of particular relevance in the context of orally consumable compositionsare Aspergillus niger, Brettanomyces bruxellensis, Brettanomycesnaardenensis, Dekkera bruxellensis, Dekkera naardenensis, Saccharomycescerevisiae, Zygosaccharomyces bailii, Zygosaccharomyces bisporus,Zygosaccharomyces florentinus, and Zygosaccharomyces rouxii.

The yeasts of the Zygosaccharomyces genus have had a long history asspoilage yeasts within the food industry. This is due mainly to the factthat these species can grow in the presence of high sucrose, ethanol,acetic acid, sorbic acid, benzoic acid, and sulphur dioxideconcentrations (which are some of the commonly used preservatives inorally consumable compositions).

Clostridium botulinum is a Gram-positive bacterium that produces severaltoxins, inter alia neurotoxins that cause the flaccid muscular paralysisseen in botulism. Botulism poisoning can occur due to improperlypreserved food or canned food that was not processed using correctpreservation times and/or pressure. Mainly slightly acidic or neutralfood is at risk which was stored under anaerobic conditions (generallypH>4.6) and storage temperatures above 10° C. The latter is generallygiven for canned foods, such as meat and fish preserves, mayonnaise, butalso slightly acidic fruit or vegetables.

Bacillus cereus may be harmful to humans and cause foodborne illness(severe nausea, vomiting and diarrhea), particularly in foods like meat,milk, spices, seasonings, fruits, vegetables, cereal and cerealproducts, rice products and (ready-to-eat) rice dishes. Bacillus cereusis also known to cause chronic skin infections and keratitis.

Bacillus subtilis is known to cause disease in severelyimmunocompromised patients, and it may cause food poisoning. Bacillussubtilis spores can survive the extreme heat during cooking. Bacillussubtilis strains are responsible for causing ropiness in spoiled breaddough.

Micrococcus luteus is found in soil, dust, water and air, and is part ofthe normal flora of the mammalian skin and mucosae. It is further a foodspoiling bacterium and often found on spoiled meat. In immunocompromisedpatients, Micrococcus luteus may cause infections.

Propionibacterium acnes is largely commensal and part of the healthyadult human skin flora. It lives primarily on fatty acids in sebumsecreted by sebaceous glands in the follicles and is linked to the skincondition acne. Propionibacterium acnes can also cause chronicblepharitis and endophthalmitis, the latter particularly followingintraocular surgery.

Dental plaque is a biofilm formed by colonizing bacteria trying toattach themselves to a smooth tooth surface. A microorganismsignificantly contributing dental plaque and tooth decay isStreptococcus mutans.

The rice blast fungus Magnaporthe grisea (syn.: Pyricularia olyzae;conidial stage/anamorph: Pyricularia grisea) attacks leaves, grains, andother parts of rice plants.

Athlete's foot (tinea pedis) is a communicable disease caused byparasitic molds in the genus Trichophyton, predominantly Trichophytonrubrum and/or Trichophyton mentagrophytes. These can also cause skininfections on other areas of the body, most often under toenails(onychomycosis) or on the groin (tinea cruris).

Mucor species are often involved in the composting of plants and plantresidues and are found on foods such as milk, butter, cheese andtomatoes. Mucor plumbeus has a worldwide distribution in soil. Asspoilage germ, Mucor plumbeus is mainly found on fermented foods (suchas bread, beer, wine, cheese, yoghurt, kefir, salami), and on grain.

Mucormycosis (sometimes also referred to as Zygomycosis) is the termused to describe fungal infections caused by fungi in the orderMucorales, inter alia by species in the Mucor genus. These rare yetserious and potentially life-threatening fungal infections usuallyaffect the face, oropharyngeal (nose/mouth) cavity, gastrointestinaltract or the skin. Individuals with immune disorders (immunocompromised)are more prone to this type of fungal infection.

Rhizopus is a genus of fungi found on plants and on various otherorganic substrates, including mature fruits and vegetables, jellies,syrups, bread, peanuts and tobacco. Some Rhizopus species areopportunistic agents of human zygomycosis (fungal infection) and can befatal. Rhizopus infections are also an associated complication ofdiabetic ketoacidosis.

Rhizopus arrhizus is the most common cause of mucormycosis in humans andoccasionally infects other animals.

Rhizopus nigricans is a fungus commonly known as bread mold and is themost common species of Rhizopus. It is found on old food. The spores,dispersed in hot dry weather, contain allergenic proteins, which canproduce respiratory and nasal symptoms. Food handling workers areparticularly at risk if they are mold allergic.

Rhizopus stolonifer (black bread mold) is a widely distributed mold andis most commonly found growing on bread and soft fruits such as bananasand grapes, and causes damage to the surface where it lives. It iscapable of causing opportunistic infections of humans.

Staphylococcus aureus is the most common species to cause staphylococcalinfections. Staphylococcus aureus can cause a range of illnesses, fromminor skin infections to life-threatening diseases such as pneumonia,meningitis, osteomyelitis, endocarditis, toxic shock syndrome,bacteremia, and sepsis. Staphylococcus aureus strains are alsoresponsible for food poisoning through the production of an enterotoxin,particularly in meat, meat products (e.g. luncheon meats, cold meats,sausages), milk, milk products, such as cheese).

Clostridium perfringens is widely present in nature and can be found asa normal component of decaying vegetation, but also in the intestinaltract of humans. Clostridium perfringens bacteria often cause offoodborne illness, particularly in poorly prepared meat and poultry.Often, meat is well prepared, but too far in advance of consumption.Since Clostridium perfringens forms spores that can withstand cookingtemperatures, upon standing or storage germination ensues and infectivebacterial colonies develop. Clostridium perfringens causes a wide rangeof symptoms: it is a very common cause of food poisoning and the mostcommon bacterial agent for gas gangrene, which is necrosis, putrefactionof tissues, and gas production.

Fungi of the genus Aspergillus may cause infections causing a variety ofdiseases called aspergillosis (common forms are allergicbronchopulmonary aspergillosis, pulmonary aspergilloma and invasiveaspergillosis).

Aspergillus flavus is a common mold in the environment, and can causestorage problems in stored grains. It can also be a human pathogen,associated with aspergillosis and other infections.

Aspergillus fumigatus is one of the most common Aspergillus species tocause disease in individuals with an immunodeficiency. Inimmunocompromised individuals, such patients receiving immunosuppressivetherapy for autoimmune or neoplastic disease, organ transplantrecipient, and people with AIDS or leukemia, the fungus is more likelyto become pathogenic and cause aspergillosis. Aspergillus fumigatusprimarily causes invasive infection in the lung (e.g. chronic pulmonaryinfections) and represents a major cause of morbidity and mortality inthese individuals.

Aspergillus niger causes black mold on certain fruits and vegetablessuch as grapes, onions, and peanuts, and is a common contaminant offood. For example, Aspergillus niger causes a common postharvest diseaseof onions. Aspergillus niger is less likely to cause human disease thansome other Aspergillus species, but, if large amounts of spores areinhaled, a serious lung disease (aspergillosis can occur). Aspergillusniger is one of the most common causes of otomycosis (fungal earinfections).

Chlamydia infection is one of the most common sexually transmittedinfections in humans, and caused by the bacterium Chlamydia trachomatis.Chlamydia is a major infectious cause of human genital and eye disease.Chlamydia conjunctivitis or trachoma is a common cause of blindnessworldwide. Both sexes can display urethritis, proctitis, trachoma, andinfertility. If untreated, chlamydial infections can cause serioushealth problems. Chlamydia trachomatis is also an important neonatalpathogen, where it can lead to infections of the eye (trachoma) andpulmonary complications.

Enterococcus faecalis inhabits the gastrointestinal tracts of humans andother mammals. It may cause endocarditis and bacteremia, urinary tractinfections, meningitis, and other infections in humans (e.g. in rootcanal-treated teeth). It can even cause life-threatening infections inhumans, especially in hospital environment.

Listeria may be been found in uncooked meats, uncooked vegetables,fruit, pasteurized or unpasteurized milk, foods made from milk, andprocessed foods. Pasteurization and sufficient cooking kill Listeria;however, contamination may occur after cooking and before packaging. Forexample, processing plants producing ready-to-eat foods, such as hotdogs, deli meats, fish products, cheeses, milk, and deli salads, followextensive sanitation policies and procedures to prevent Listeriacontamination. The major human pathogen in the Listeria genus isListeria monocytogenes. It is usually the causative agent oflisteriosis, a serious bacterial infection caused by eating foodcontaminated with Listeria monocytogenes.

Yeasts of the Candida genus are a group of opportunistic pathogens thatcauses oral and vaginal infections in humans, known as candidiasis. Thepathogenic yeasts of candidiasis are Candida albicans, Candidatropicalis, Candida stellatoidea, Candida glabrata, Candida krusei,Candida parapsilosis, Candida guilliermondii, Candida viswanathii, andCandida lusitaniae, of these Candida albicans being the most importantand most relevant.

Candida glabrata is the second most common Candida pathogen afterCandida albicans, also causing infections of the urogenital tract, andof the bloodstream (candidemia). Candida glabrata has been shown to be ahighly opportunistic pathogen and is especially prevalent inimmunocompromised individuals and elderly. Candida glabrata can alsoadhere to biotic and abiotic surfaces, thereby forming microbial“biofilms” on e.g. urinary catheters or indwelling intravenouscatheters. It may also cause problems with dental devices, such asdentures.

Additionally, in particular Staphylococcus aureus, Candida albicans,Aspergillus brasiliensis and Aspergillus niger are likelymicrobiological contaminants of cosmetic formulations.

Species of certain bacteria such as Staphylococcus epidermidis,Corynebacterium xerosis, Corynebacterium minutissimum and Brevibacteriumepidermidis are largely responsible for the formation of underarm and/orfoot odor, or body odor in general. Brevibacterium linens inter aliacauses foot odor.

In another aspect the present invention relates to one or more compoundsof formula I and/or the physiologically acceptable salts thereof,particularly one or more compounds selected from the group consisting of[1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13],[14], [18], [19], [20], [21] and the physiologically acceptable saltsthereof, for use in the prophylactic and/or therapeutic treatment of adisorder, disease or condition selected from the group consisting of

mycoses (fungal infections), preferably Aspergillus, Candida or Mucorassociated mycoses, particularly Candida associated mycoses.

Particularly relevant and preferably treated are mycoses selected fromthe group consisting of candidiasis [in particular oral (thrush) Candidainfections, infections of the urogenital (e.g. vaginal) tract by Candidabacteria (in particular by Candida albicans and/or Candida glabrata),diaper candidiasis (Candida associated diaper dermatitis, diaper rash)],invasive candidiasis (particularly candidemia (infections of thebloodstream)), aspergillosis and mucormycosis.

The compounds of formula I and/or the physiologically acceptable saltsthereof, particularly those selected from the group consisting of [1],[2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14],[18], [19], [20], [21] and the physiologically acceptable salts thereof,are particularly beneficial for use in the prophylactic treatment of adisorder, disease or condition mentioned above.

As used herein, the term “effective amount” or “effective dose” refersto the (preferably oral) administration of an effective dose of one ormore compounds of formula I and/or the physiologically acceptable saltsthereof that produces the effects for which it is administered.

As used herein, the term “therapeutical” or “therapeutically” refers tothe (in particular oral) administration of a therapeutically effectivedose of one or more compounds of formula I and/or the physiologicallyacceptable salts thereof (preferably in form of a mixture, a compositionor a material as defined in the context of the present invention) thatproduces the effects for which it is administered, i.e. that will elicitthe biological or medical response (in vitro or in vivo, preferably invivo in a mammal, particularly in vivo in human being) that is beingsought, in particular the amelioration and/or alleviation of thesymptoms of the disorder, disease or condition being treated up to andincluding complete cure.

As used herein, the term “prophylactic” or “prophylactically” refers tothe (in particular oral) administration of a prophylactically effectivedose of one or more compounds of formula I (preferably in form of amixture, a composition or a material as defined in the context of thepresent invention) that produces the effects for which it isadministered, i.e. that will elicit the biological or medical response(in vitro or in vivo, preferably in vivo in a mammal, particularly invivo in a human being) that is being sought, in particular theprevention of the onset of a disorder, disease or condition inindividuals at risk for such disorder, disease or condition as mentionedherein.

The present invention also relates to a method of reducing the activityand/or number of pathogenic Gram-positive bacteria and/or pathogenicfungi in an immunocompromised individual, comprising the following step:

administering (preferably orally or topically) to a mammal, particularlyan immunocompromised mammal, particularly an immunosuppressed humanbeing, an effective total amount of

-   -   one or more compounds of formula I as defined herein, and/or one        or more physiologically acceptable salts thereof, particularly        one or more compounds selected from the group consisting of [1],        [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13],        [14], [18], [19], [20], [21] and the physiologically acceptable        salts thereof,        or    -   an extract or material according to the present invention,        preferably in a preferred or particularly preferred embodiment        according to the present invention.

Preferably, the pathogenic Gram-positive bacteria are selected from thegroup consisting of the genera Bacillus, Clostridium, Listeria,Micrococcus and Staphylococcus, more preferably selected from the groupconsisting of Bacillus cereus, Clostridium sporogenes, Clostridiumperfringens, Listeria monocytogenes, Micrococcus luteus, Staphylococcusaureus, Staphylococcus epidermidis.

Preferably, the pathogenic fungi are selected from the group consistingof the genera Aspergillus and Candida, more preferably selected from thegroup consisting of Aspergillus flavus, Aspergillus fumigatus, Candidaalbicans, Candida glabrata, Candida lusitaniae, and Candida tropicalis.

The present invention also relates to a method for the prophylacticand/or therapeutic treatment of a disease, disorder or condition,comprising the following step:

administering (preferably orally or topically) to a mammal, particularlyan immunocompromised mammal, particularly an immunosuppressed humanbeing, an effective total amount of

-   -   one or more compounds of formula I as defined herein, and/or one        or more physiologically acceptable salts thereof, particularly        one or more compounds selected from the group consisting of [1],        [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13],        [14], [18], [19], [20], [21], and the physiologically acceptable        salts thereof,        or    -   an extract or material according to the present invention,        preferably in a preferred or particularly preferred embodiment        according to the present invention.

The compounds of formula I (for use) according to the present inventionand/or the physiologically acceptable salts thereof (preferably thepreferred or particularly preferred compounds of formula I definedabove) show a comparatively weak activity against Gram-negativebacteria, such as Escherichia coli, Pseudomonas aeruginosa, Pseudomonasputida or Salmonella typhimurium. In our own investigations regardingsuch Gram-negative bacteria generally MIC values >100 ppm were observed,typically in the range of 200-500 ppm.

Thus, in a preferred embodiment, a material according to the presentinvention, preferably a cosmetic or a pharmaceutical, comprises (i) oneor more compounds of formula I (for use) according to the presentinvention and/or the physiologically acceptable salts thereof, and (ii)one or more agents exhibiting an antimicrobial activity againstGram-negative bacteria, preferably selected from the group consisting ofTriclosan® (2,4,4′-trichloro-2′-hydroxydiphenyl ether), chlorhexidine,chlorhexidine salts (preferably chlorhexidine diacetate, chlorhexidinedichloride, chlorhexidine digluconate), octenidine, octenidinedihydrochloride, 2-bromo-2-nitropropane-1,3-diol, polyaminopropylbiguanide, imidazolidinyl urea, diazolidinyl urea, chlorphenesin, DMDMhydantoin, sodium hydroxymethylglycinate, phenoxyethanol,isothiazolinones (preferably methylisothiazolinone,methylchloroisothiazolinone), benzalkonium chloride(alkyldimethylbenzylammonium chloride, preferablyN-octyl-N-benzyl-N,N-dimethylammonium chloride,N-decyl-N-benzyl-N,N-dimethylammonium chloride,N-dodecyl-N-benzyl-N,N-dimethylammonium chloride,N-tridecyl-N-benzyl-N,N-dimethylammonium chloride,N-tetradecyl-N-benzyl-N,N-dimethylammonium chloride,N-hexadecyl-N-benzyl-N,N-dimethylammonium chloride,N-octadecyl-N-benzyl-N,N-dimethylammonium chloride), and lantibiotics(preferably those disclosed in U.S. Pat. No. 7,960,505 B2).

In some cases, a material according to the present invention, preferablya cosmetic or a pharmaceutical, comprises (i) one or more compounds offormula I (for use) according to the present invention and/or thephysiologically acceptable salts thereof, and (ii) one or more parabens(para-hydroxybenzoic acid esters) and/or the salts thereof, preferablyone, two or more parabens selected from the group consisting ofmethylparaben, ethylparaben, propylparaben, isopropylparaben,butylparaben, isobutylparaben, benzylparaben and the physiologicallyacceptable salts (preferably the sodium salts) thereof.

Compounds of the formula I, mixtures thereof, and the physiologicallyacceptable salts thereof are preferred in the context of the presentinvention, wherein R is a moiety of formula

whereinR^(z) denotes H or C₂-C₆-alkanoyl, preferably H, acetyl or C₅-alkanoyl,more preferably H, acetyl or isovaleryl, most preferably isovaleryl,R^(y) denotes H or C₂-C₆-alkanoyl, preferably H or acetyl,and R^(x), independent of each other, each denote H or C₂-C₆-alkanoyl,preferably H or acetyl, with the proviso that at least one of R^(x),R^(y) and R^(z) is not hydrogen.

Compounds of the formula I, mixtures thereof, and the physiologicallyacceptable salts thereof are more preferred in the context of thepresent invention, wherein R is a moiety of formula

whereinR^(z) denotes H, acetyl or isovaleryl, most preferably isovaleryl,R^(y) denotes H or C₂-C₆-alkanoyl, preferably H or acetyl,and R^(x), independent of each other, each denote H or C₂-C₆-alkanoyl,preferably H or acetyl,with the proviso that at least one of R^(y) and R^(z) is not hydrogen,preferably R^(z) is not hydrogen.

Individual compounds of formula I with an acyl substituent with morethan 2 carbon atoms, such as an isovaleryl substituent, in thetrisaccharide carbohydrate moiety R exhibit a stronger antimicrobialactivity, particularly against yeasts and molds, especially againstyeasts and molds of relevance regarding food, beverage and/or cosmeticspoilage, and/or a broader activity spectrum than the correspondingcompounds with an acetyl substituent in the trisaccharide carbohydratemoiety R.

It was also found in own investigations that mixtures comprising (i)two, three, four, five, six or more compounds of the above preferredformula I, (ii) two, three, four, five, six or more physiologicallyacceptable salts of a compound of the above preferred formula I, or amixture thereof, or (iii) one, two, three or more compounds of the abovepreferred formula I and one, two, three or more physiologicallyacceptable salts of a compound of the above preferred formula Itypically showed a broader activity spectrum and/or stronger long terminhibitory activity, particularly against yeasts and molds, especiallyagainst yeasts and molds of relevance regarding food, beverage and/orcosmetic spoilage, in comparison to individual compounds of (preferred)formula I or a physiologically acceptable salt thereof.

Said stronger long term inhibitory activity—which typically isbactericidal and/or fungicidal, and not merely bacteriostatic and/orfungistatic) and/or broader long term inhibitory activity spectrum ofmixtures according to the present invention against organisms involvedin spoilage of preparations or compositions with a high water content(generally 50 wt. % or more, based on the total weight of thepreparation or composition) is especially useful against acidophilicspoilage yeasts, which are for example involved in spoiling ofbeverages. These mixtures according to the present invention areparticularly able to inhibit the growth of thermophilic molds, which aredifficult to control with standard sterilizing and/or pasteurizingprocesses.

Especially preferred in the context of the present invention in view ofthe excellent properties is a mixture of three or more compounds offormula I or the physiologically acceptable salts thereof, said mixturecomprising

(a) one or more compounds of formula I or a physiologically acceptablesalt thereof, wherein one group of R^(x), R^(y), and R^(z) is nothydrogen,(b) one or more compounds of formula I or a physiologically acceptablesalt thereof wherein two groups of R^(x), R^(y), and R^(z) are nothydrogen, and(c) one or more compounds of formula I or a physiologically acceptablesalt thereof wherein three groups of R^(x), R^(y), and R^(z) are nothydrogen,wherein preferably

-   -   the total amount of the compounds of group (a) is 2 wt. % or        more, preferably 3 wt. % or more, more preferably 5 wt. % or        more, in each case based on the total weight of the mixture,    -   and/or    -   said mixture comprises one, two, three or all compounds [5],        [8], [12], and [14],        and/or    -   the total amount of the compounds of group (b) is 20 wt. % or        more, preferably 25 wt. % or more, more preferably 30 wt. % or        more, even more preferably 35 wt. % or more, most preferably 40        wt. % or more, in each case based on the total weight of the        mixture,    -   and/or    -   said mixture comprises one, two, three, four, five or all        compounds [1], [6], [7], [10], [13], and [18], more preferably        comprises [1] and/or [7], particularly more preferably [1] and        [7],    -   and/or    -   said mixture comprises compound [1], preferably in a total        amount of 1 wt. % or more, more preferably 2 wt. % or more, even        more preferably 4 wt. % or more, particularly preferably 5 wt. %        or more,    -   and/or    -   said mixture comprises compound [7], preferably in a total        amount of 5 wt. % or more, more preferably 8 wt. % or more, even        more preferably 10 wt. % or more, particularly preferably 12 wt.        % or more,        and/or    -   the total amount of the compounds of group (c) is 1 wt. % or        more, preferably 1.5 wt. % or more, more preferably 2 wt. % or        more, in each case based on the total weight of the mixture,    -   and/or    -   said mixture comprises [3] and/or [9], preferably compound [9].

In a preferred mixture according to the present invention, preferablythe average degree of acylation is as follows:

1.1 to 2.2 acetyl groups per molecule, preferably 1.3 to 1.9 acetylgroups per molecule,and/or0.1 to 1.0 isovaleryl groups per molecule, preferably 0.15 to 0.6isovaleryl groups per molecule,wherein the average degree of acylation preferably is determined via¹H-NMR quantification using an average molecular weight for theglycolipids of 985 g/mol. As internal standard preferably1,3,5-trichlorbenzene may be used. The ¹H-NMR signal used for saidquantification was that of the hydrogen atom bound to the carbon atom inposition C-2 (i.e. (CH)OH, the carbon atom bearing the alpha-hydroxygroup relative to the carboxylic acid group at C-1).

A mixture according to the present invention, an extract according tothe present invention, a material according to the present invention,and/or a composition according to the present invention preferablycomprises less than 25 wt. % of Glykenin IVA((2S,16R,17S,21R)-2,16,17-trihydroxy-21-[[2-O-[2-O-(6-O-acetyl-β-D-glucopyranosyl)-β-D-xylopyranosyl]-4-O-acetyl-β-D-xylopyranosyl]oxy]hexacosanoicacid), more preferably less than 20 wt. % of Glykenin IVA, particularlypreferably less than 15 wt. % of Glykenin IVA, in each case based on thetotal amount of compounds of formula I and the physiologicallyacceptable salts thereof.

Preferably, a mixture comprises compounds [1] and [7], and thephysiologically acceptable salts thereof, wherein more preferably thetotal amount of

compound [1] and the physiologically acceptable salts thereof is 1 wt. %or more, more preferably 2 wt. % or more, more preferably 3 wt. % ormore,and/orcompound [7] and the physiologically acceptable salts thereof is 1 wt. %or more, more preferably 2 wt. % or more, more preferably 3 wt. % ormore,and/orthe compounds [1] and [7], and the physiologically acceptable saltsthereof is 5 wt. % or more, more preferably 8 wt. % or more, even morepreferably 12 wt. % or more,the weight percentages in each case relating to the total weight of themixture,

More preferably, a mixture according to the present invention comprises

a total amount of 1-20 wt. %, preferably 2-15 wt. %, of compound [1] andthe physiologically acceptable salts thereof,a total amount of 0-10 wt. %, preferably 0.5-5 wt. %, of compound [5]and the physiologically acceptable salts thereof,a total amount of 0-10 wt. %, preferably 0.5-5 wt. %, of compound [6]and the physiologically acceptable salts thereof,a total amount of 2-75 wt. %, preferably 5-50 wt. %, of compound [7] andthe physiologically acceptable salts thereof,a total amount of 0-12 wt. %, preferably 1-8 wt. %, of compound [8] andthe physiologically acceptable salts thereof,a total amount of 0-12 wt. %, preferably 1-8 wt. %, of compound [9] andthe physiologically acceptable salts thereof,a total amount of 0-12 wt. %, preferably 1-10 wt. %, of compound [10]and the physiologically acceptable salts thereof,a total amount of 0-10 wt. %, preferably 0.5-6 wt. %, of compound [12]and the physiologically acceptable salts thereof,a total amount of 0-8 wt. %, preferably 0.25-4 wt. %, of compound [13]and the physiologically acceptable salts thereof,a total amount of 0-8 wt. %, preferably 0.25-5 wt. %, of compound [18]and the physiologically acceptable salts thereof,and additionally preferably one, several or all of the following furtherparameters apply:

-   -   said mixture comprises a total amount of compounds of formula I        and the physiologically acceptable salts thereof of 75 wt. % or        more, preferably 80 wt. % or more, more preferably 85 wt. % or        more,    -   said mixture comprises less than 8 wt. %, preferably less than 6        wt. %, more preferably less than 4 wt. %, of compounds of        formula I without any acyl substituents in the trisaccharide        carbohydrate moiety R (particularly less than 2.0 wt. % of        compound [16]),    -   said mixture comprises Glykenin IVA in an amount of 25 wt. % or        less, preferably of 20 wt. % or less, more preferably of 15 wt.        % or less,    -   said mixture comprises proteins in a total amount of 2 wt. % or        less, preferably of 1.25 wt. % or less, more preferably of 1.0        wt. % or less,        and/or    -   said mixture comprises water in a total amount of 4 wt. % or        less, preferably of 3 wt. % or less, more preferably of 2 wt. %        or less,        the percentages in each case relating to the total weight of the        mixture.

Particularly preferably, a mixture according to the present inventioncomprises

a total amount of 3-15 wt. %, of compound [1] and the physiologicallyacceptable salts thereof,a total amount of 0.5-5 wt. % of compound [5] and the physiologicallyacceptable salts thereof,a total amount of 0.5-5 wt. % of compound [6] and the physiologicallyacceptable salts thereof,a total amount of 10-35 wt. % of compound [7] and the physiologicallyacceptable salts thereof,a total amount of 1-8 wt. % of compound [8] and the physiologicallyacceptable salts thereof,a total amount of 1-8 wt. % of compound [9] and the physiologicallyacceptable salts thereof,a total amount of 1-10 wt. % of compound [10] and the physiologicallyacceptable salts thereof,a total amount of 0.5-6 wt. % compound [12] and the physiologicallyacceptable salts thereof,a total amount of 0.25-4 wt. % of compound [13] and the physiologicallyacceptable salts thereof, anda total amount of 0.25-5 wt. % of compound [18] and the physiologicallyacceptable salts thereof,and additionally preferably one, two, three, four or all of thefollowing further parameters apply:

-   -   said mixture comprises a total amount of compounds of formula I        and the physiologically acceptable salts thereof of 85 wt. % or        more, more preferably of 90 wt. % or more,    -   said mixture comprises less than 5 wt. %, preferably less than 3        wt. %, of compounds of formula I without any acyl substituents        in the trisaccharide carbohydrate moiety R (particularly less        than 1.0 wt. % of compound [16]),    -   said mixture comprises Glykenin IVA in an amount of 20 wt. % or        less, preferably of 15 wt. % or less,    -   said mixture comprises proteins in a total amount of 1.25 wt. %        or less, preferably of 0.95 wt. % or less.        and/or    -   said mixture comprises water in a total amount of 3 wt. % or        less, preferably of 2 wt. % or less,        the percentages in each case relating to the total weight of the        mixture.

Such a particularly preferred mixture according to the present inventionhad the following average degree of acylation:

1.4 to 1.8 acetyl groups per molecule, and0.2 to 0.5 isovaleryl groups per molecule.

In view of their broad activity spectrum and particularly high efficacy(which was found to be superior to otherwise identical compounds offormula I not carrying a hydroxyl group esterified with isovalericacid), particularly against yeasts and molds, especially against yeastsand molds of relevance regarding food, beverage and/or cosmeticspoilage, the compounds of formula I, mixtures thereof, and thephysiologically acceptable salts thereof are especially preferred in thecontext of the present invention wherein

m is 3, 4 or 5, n is 3, o is 0 or 1 and p is 11 to 14 (preferably p is12 or 13), andR is a moiety of formula

whereinR^(y) denotes H or C₂-C₆-alkanoyl, preferably H or acetyl,and R^(x), independent of each other, each denote H or C₂-C₆-alkanoyl,preferably H or acetyl.

Particularly preferred are compounds of formula I of the followingformulae

more preferably of the following formulae

wherein in each of said formulaeR^(y) denotes H or C₂-C₆-alkanoyl, preferably H or acetyl,and each R^(x), independently of the other R^(x), denotes H orC₂-C₆-alkanoyl, preferably H or acetyl.

Particularly preferred are the following compounds of formulae [1a],[12a], [13a], [18a], [19a], [20a], and [21a], mixtures thereof, and thephysiologically acceptable salts thereof

Particularly preferred are the following compounds of formulae [1b],[12b], [13b] and [18b], mixtures thereof, and the physiologicallyacceptable salts thereof

Particularly preferred are the following compounds of formulae [1c],[12c], [13c] and [18c], mixtures thereof, and the physiologicallyacceptable salts thereof

In a preferred embodiment, the present invention relates to acomposition comprising or consisting of three, four, five, six, seven,eight, nine, ten, eleven, twelve or more compounds of formula I,

wherein the total amount of said compounds of formula I is greater than75 wt. %, preferably greater than 80 wt. %, more preferably greater than85 wt. %, particularly preferably greater than 90 wt. %, in each casebased on the total weight the composition,and preferably

-   -   a total amount of 90 wt. % or less, more preferably of 75 wt. %        or less, even more preferably of 50 wt. % or less, particularly        preferably of 25 wt. % or less, especially preferably of 10 wt.        % or less, and most preferably of 5 wt. % or less of liquid (at        25° C. and 1013 mbar) diluents, in particular water, in each        case based on the total weight of the composition,        and/or    -   a total amount of 5 wt. % or less, more preferably of 2 wt. % or        less, particularly preferably of 1.25 wt. % or less, and most        preferably of 0.8 wt. % or less of proteins, in each case based        on the total weight of the composition,        and/or    -   a total amount of 5 wt. % or less, more preferably of 3 wt. % or        less, particularly preferably of 2 wt. % or less of sugar        alcohols and mono- or disaccharides, in each case based on the        total weight of the composition,        and/or    -   a total amount of 5 wt. % or less, more preferably of 4 wt. % or        less, even more preferably of 3 wt. % or less, particularly        preferably of 2 wt. % or less, most preferably of 1 wt. % or        less of cells and cell material with a size in at least one        dimension of greater than 3 micrometer (μm), preferably with a        size in at least one dimension of greater than 2 μm, more        preferably with a size in at least one dimension of greater than        1 μm, of fungi of the Dacrymycetaceae family, in each case based        on the total weight of the composition.

In a particularly preferred embodiment, the present invention relates toa composition comprising or consisting of one or more, preferably two,three, four, five, six, seven, eight, nine, ten, eleven, twelve or morephysiologically acceptable salts of one or more, preferably two, three,four, five, six, seven, eight, nine, ten, eleven, twelve or morecompounds of formula I,

wherein the total amount of said physiologically acceptable salts of thecompounds of formula I is greater than 70 wt. %, preferably greater than80 wt. %, more preferably greater than 90 wt. %, particularly preferablygreater than 95 wt. %, in each case based on the total amount ofcompounds of formula I and the physiologically acceptable salts thereof,and preferably

-   -   a total amount of 90 wt. % or less, more preferably of 75 wt. %        or less, even more preferably of 50 wt. % or less, particularly        preferably of 25 wt. % or less, especially preferably of 10 wt.        % or less, and most preferably of 5 wt. % or less of liquid (at        25° C. and 1013 mbar) diluents, in particular water, in each        case based on the total weight of the composition,        and/or    -   a total amount of 5 wt. % or less, more preferably of 3 wt. % or        less, particularly preferably of 2 wt. % or less, and most        preferably of 1 wt. % or less of proteins, in each case based on        the total weight of the composition,        and/or    -   a total amount of 20 wt. % or less, more preferably of 15 wt. %        or less, particularly preferably of 10 wt. % or less, most        preferably of 5 wt. % or less of sugar alcohols and mono- or        disaccharides, in each case based on the total weight of the        composition,        and/or    -   a total amount of 5 wt. % or less, more preferably of 4 wt. % or        less, even more preferably of 3 wt. % or less, particularly        preferably of 2 wt. % or less, most preferably of 1 wt. % or        less of cells and cell material with a size in at least one        dimension of greater than 10 micrometer (μm), preferably with a        size in at least one dimension of greater than 5 μm, more        preferably with a size in at least one dimension of greater than        3 μm, most preferably with a size in at least one dimension of        greater than 2 μm, of fungi of the Dacrymycetaceae family, in        each case based on the total weight of the composition.

In a especially preferred embodiment, the present invention relates to acomposition comprising or consisting of three, four, five, six, seven,eight, nine, ten, eleven, twelve or more physiologically acceptablesalts of one or more, preferably two, three, four, five, six, seven,eight, nine, ten, eleven, twelve or more compounds of formula I,

wherein the total amount of said physiologically acceptable salts of thecompounds of formula I is greater than 85 wt. %, more preferably greaterthan 90 wt. %, particularly preferably greater than 95 wt. %, in eachcase based on the total amount of compounds of formula I and thephysiologically acceptable salts thereof,and additionally

-   -   a total amount of 25 wt. % or less, preferably of 10 wt. % or        less, and particularly preferably of 5 wt. % or less of water,        in each case based on the total weight of the composition,    -   a total amount of 2 wt. % or less, preferably of 1 wt. % or less        of proteins, in each case based on the total weight of the        composition,    -   a total amount of 10 wt. % or less, most preferably of 5 wt. %        or less of sugar alcohols and mono- or disaccharides, in each        case based on the total weight of the composition,        and    -   a total amount of 2 wt. % or less, most preferably of 1 wt. % or        less of cells and cell material with a size in at least one        dimension greater than 2 μm, more preferably with a size in at        least one dimension of greater than 1 μm, most preferably with a        size in at least one dimension of greater than 0.7 μm of fungi        of the Dacrymycetaceae family, in each case based on the total        weight of the composition.

Preferably, the determination of the total amount of nitrogen and thetotal protein content is performed according to the Kjeldahl method,preferably according to ISO 5549: 1978.

It was found in our own investigations that said preferred orparticularly preferred compositions according to the present inventioncomprising one or more physiologically acceptable salts of one or morecompounds of formula I show improved, in particular longer, storagestability in comparison to the corresponding compounds of formula I infree acid form. It was also found in our own investigations that suchcompositions have a superior, i.e. higher, solubility inaqueous-alcoholic solvents or water in comparison to the correspondingcompounds of formula I in free acid form. For example, while it is notpossible to obtain a stable 1 wt. % solution of a mixture of compoundsof formula I in free acid form in water, it is easily possible toproduce a 10 wt. % solution of a mixture of compounds of formula I intheir salt form. Thus, the one or more physiologically acceptable saltsof one or more compounds of formula I have excellent formulationproperties, in particular regarding aqueous food, beverage and cosmeticmaterials, in particular with a water content of 50 wt. % or more, whichare superior in comparison to the corresponding compounds of formula Iin free acid form. Additionally, said compositions and solutions showedvery good skin compatibility.

Particularly preferably, the trisaccharide carbohydrate moiety R in thecompounds of formula I—without including any substituents resulting fromacylation of hydroxyl groups of said trisaccharide carbohydrate moietyR—is abeta-D-glucopyranosyl-(1→2)-beta-D-xylopyranosyl-(1→2)-beta-D-xylopyranosidemoiety. Further, of said trisaccharide carbohydrate moiety R preferablyone, two, three or four hydroxyl groups are esterified by aC₂-C₁₀-alkanoic acid, i.e. said trisaccharide carbohydrate moiety Rbeing in mono- or di- or tri- or tetra-acylated form (i.e. esterifiedwith an C₂-C₁₀-alkanoic acid). It was found in our own investigationsthat compounds of formula I without any acyl substituents in thetrisaccharide carbohydrate moiety R (such as compound [16]) showedsignificantly inferior antimicrobial activities, in particular regardingGram-positive bacteria, but also to a noticeable extent regarding yeastsand molds.

Therefore, a mixture according to the present invention, an extractaccording to the present invention, a material according to the presentinvention, and/or a composition according to the present inventionpreferably comprises less than 15 wt. % of compounds of formula Iwithout any acyl substituents in the trisaccharide carbohydrate moiety R(particularly compound [16]), more preferably less than 10 wt. %,particularly preferably less than 5 wt. %, in each case based on thetotal amount of compounds of formula I and the physiologicallyacceptable salts thereof.

In a particularly preferred embodiment relates to the compounds of theformula I carrying one, two, three or four acylated hydroxyl groups inthe trisaccharide carbohydrate moiety R, said acyl moiety preferablybeing a C₃-C₆-alkanoic acid, more preferably an isovaleryl(3-methyl-butanoyl) moiety. These compounds were found to exhibitsuperior antimicrobial activity regarding certain Gram-positive bacteriaand regarding fungi, yeasts and molds.

Preferably, such a mixture comprises, essentially consists of orconsists of alkali and/or alkaline earth salts of two or more compoundsof formula I, more preferably of sodium and/or potassium and/or calciumand/or magnesium salts thereof, in particular the sodium and/orpotassium and/or calcium and/or magnesium salts of one, two, three,four, five, six, seven, eight, nine or more of the compounds selectedfrom the group consisting of compounds [1], [4], [5], [6], [7], [8],[9], [10], [12], [13], [14], and [18], wherein the total amount of waterpreferably is less than 5 wt. %, more preferably less than 3 wt. %, andparticularly preferably less than 1 wt. %, in each case based on thetotal weight of the mixture.

Preferably such a mixture comprises the sodium and/or potassium and/orcalcium and/or magnesium salts of one, two, three, four, five, six,seven, eight or more of the compounds selected from the group consistingof [1], [4], [5], [6], [7], [8], [9], [10], [12], [13], [14], and [18],wherein the total amount of salts of the compounds of formula I isgreater than 70 wt. %, preferably greater than 75 wt. %, more preferablygreater than 80 wt. %, particularly preferably greater than 85 wt. %, ineach case based on the total weight of the mixture.

Particularly preferably such a mixture comprises the sodium and/orpotassium and/or calcium and/or magnesium salts of one, two, three, fouror all of the compounds selected from the group consisting of compounds[1], [7], [12], [13], and [18], wherein the total amount of said saltsof the compounds [1], [7], [12], [13], and [18] is greater than 10 wt.%, preferably greater than 15 wt. %, more preferably greater than 20 wt.%, in each case based on the total weight of the mixture.

Preferably, such a mixture according to the present invention is eitherin solid (at 25° C. and 1013 mbar) form, preferably in powder form witha total residual water content of 5 wt. % or less, preferably of 3 wt. %or less, more preferably of 1 wt. % or less, or is in the form of anaqueous or aqueous-alcoholic solution, wherein the total amountcompounds of formula I and the physiologically acceptable salts thereofis in the range of 1 to 40 wt. %, more preferably in the range of 2 to33 wt. %, even more preferably in the range of 3 to 25 wt. %, and mostpreferably in the range of 5 to 20 wt. %, in each case based on thetotal weight of the mixture.

Further purification of an extract according to the present invention, amixture according to the present invention, and in particular of acomposition comprising or consisting of one or more physiologicallyacceptable salts of one or more compounds of formula I (as definedabove) may be further purified according to methods and materialsdescribed in U.S. Pat. No. 6,051,212, WO 96/38057 and/or JP 2006-176438A, preferably centrifugation and/or filtration (includingultrafiltration and/or microfiltration), preferably using one or moresorbent (absorbent or adsorbent) materials selected from the groupconsisting of activated carbons, charcoal, ion exchange resins(preferably a weakly basic or weakly acidic ion exchange resin,macroporous ion exchange resins in turn being preferred), silica,alumina, kieselgur (diatomaceous earth, e.g. celite), glass particles,glass wool, glass fibers, zeolites (such as zeolite A, zeolite X,zeolite Y), silicates and aluminosilicates (preferably clays and clayminerals like bentonite, kaolinite, montmorillonite, smectite, illite,chlorite).

In a further aspect the present invention relates to a method ofproducing an extract comprising a compound of formula I or a mixture oftwo or more compounds of formula I (for use) according to the presentinvention, in particular a mixture comprising one or more compoundsselected from the group consisting of compounds [1], [2], [3], [4], [5],[6], [7], [8], [9], [10], [11], [12], [13], [14], [18], [19], [20], and[21], comprising the following steps:

-   -   preferably providing a fungus of the family Dacrymycetaceae,        preferably a fungus of the genera Dacryopinax, Dacrymyces,        Ditiola, Femsjonia or Guepiniopsis, more preferably a fungus of        the species Dacryopinax spathularia,    -   carrying out a fermentation process such that one, two or more        compounds of formula I are produced (preferably by said fungus        of the family Dacrymycetaceae),    -   setting the pH value of the fermentation broth to a value below        4, preferably to a pH value in the range of from 1 to 3.5, more        preferably to a pH value in the range of from 1.5 to 3,    -   keeping the resulting reaction mixture at a pH value below 4,        preferably at a pH value in the range of from 1 to 3.5, more        preferably to a pH value in the range of from 1.5 to 3, thereby        partially or essentially precipitating one, two or more        compounds of formula I, and    -   washing the resulting precipitate comprising, essentially        consisting of or consisting of one, two or more compounds of        formula I, preferably with an aqueous diluent, more preferably        with water, particularly preferably with demineralized water,    -   optionally suspending the precipitate comprising, essentially        consisting of or consisting of one, two or more compounds of        formula I in an aqueous diluent, more preferably in water,        particularly preferably in demineralized water,    -   optionally removing water from the resulting product, preferably        freeze-drying the resulting product, thereby preferably yielding        an extract comprising, essentially consisting of or consisting        of one, two or more compounds of formula I in solid (and        preferably essentially water-free) form.

In a further aspect the present invention relates to a method ofproducing one or more physiologically acceptable salts of one or morecompounds of formula I according to the present invention, in particularone or more physiologically acceptable salts of one, two or morecompounds selected from the group consisting of compounds [1], [2], [3],[4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [18], [19],[20], and [21], comprising the following steps:

-   -   providing a fungus of the family Dacrymycetaceae, preferably a        fungus of the genera Dacryopinax, Dacrymyces, Ditiola, Femsjonia        or Guepiniopsis, more preferably a fungus of the species        Dacryopinax spathularia,    -   carrying out a fermentation process such that a compound of        formula I or a mixture of two or more compounds of formula I is        produced by said fungus,    -   setting the pH value of the fermentation broth to a value below        4, preferably to a pH value in the range of from 1 to 3.5, more        preferably to a pH value in the range of from 1.5 to 3,    -   keeping the resulting reaction mixture at a pH value below 4,        preferably at a pH value in the range of from 1 to 3.5, more        preferably to a pH value in the range of from 1.5 to 3, thereby        partially or essentially precipitating a compound of formula I        or a mixture of two or more compounds of formula I,    -   preferably washing the resulting precipitate (pellet) preferably        with an aqueous diluent, more preferably with water,        particularly preferably with demineralized water,    -   suspending the resulting precipitate (pellet) in an aqueous        diluent, more preferably in water, particularly preferably in        demineralized water,    -   setting the pH value of the suspension to a value in the range        of 4.5 to 7.5, preferably in the range of 5 to 7, particularly        preferably in the range of 5.5 to 6.5, by adding an inorganic        base (solution or suspension), preferably sodium hydroxide,        potassium hydroxide, calcium hydroxide, and/or magnesium        hydroxide, and    -   removing water from the resulting product, preferably drying,        particularly freeze-drying the resulting product, thereby        obtaining one or more physiologically acceptable salts of one or        more compounds of formula I according to the present invention        as a solid, preferably a powder, and preferably in essentially        water-free form.

Preferably, the fermentation is carried out in the absence of aneffective amount of visible light (i.e. light with a wavelength in therange 380 to 750 nm), more preferably in the absence of an effectiveamount of visible light and ultraviolet light, most preferably in theabsence of an effective amount of light. Due to such measure theproduction of carotenoids, in particular beta-carotene, is minimized oravoided (in contrast to U.S. Pat. No. 2,974,044).

Preferably, the fermentation is carried out with one or more fungiselected from the group consisting of

Dacryopinax aurantiaca, Dacryopinax crenata, Dacryopinax dennisii,Dacryopinax elegans, Dacryopinax felloi, Dacryopinax fissus, Dacryopinaxfoliacea, Dacryopinax formosus, Dacryopinax imazekiana, Dacryopinaxindacocheae, Dacryopinax lowyi, Dacryopinax macrospora, Dacryopinaxmartinii, Dacryopinax maxidorii, Dacryopinax parmastoensis, Dacryopinaxpetaliformis, Dacryopinax spathularia, Dacryopinax sphenocarpa,Dacryopinax taibaishanensis, Dacryopinax xizangensis, Dacryopinaxyungensis,Dacrymyces ancyleus, Dacrymyces aureosporus, Dacrymyces australis,Dacrymyces capitatus, Dacrymyces chrysocomus, Dacrymyces chrysospermus,Dacrymyces cupularis, Dacrymyces dictyosporus, Dacrymyces enatus,Dacrymyces flabelliformis, Dacrymyces intermedius, Dacrymyces Dacrymycesmacnabbii, Dacrymyces minor, Dacrymyces novae-zelandiae, Dacrymycesovisporus, Dacrymyces paraphysatus, Dacrymyces pinacearum, Dacrymycespunctiformis, Dacrymyces stillatus, Dacrymyces subarcticus, Dacrymycestortus, Dacrymyces variisporus,Ditiola abieticola, Ditiola brasiliensis, Ditiola coccinea, Ditiolanuda, Ditiola oblique, Ditiola orientalis, Ditiola pezizaeformis,Ditiola radicata,Guepiniopsis alpina, Guepiniopsis buccina, Guepiniopsis estonica,Guepiniopsis oresbia, Guepiniopsis ovispora, Guepiniopsis pedunculata,and Guepiniopsis suecica.

In a preferred embodiment, a material according to the present inventioncomprising an above defined (preferred or particularly preferred) totalamount of water are selected from the group consisting of anO/W-emulsion, a hydrodispersion, a suspension, a solution, or ahydrogel.

Preferably, a material according to the present invention comprises ahigh proportion of water, preferably water in a total amount of 50 wt. %or more, more preferably of 60 wt. % or more, even more preferably 65wt. % or more, particularly preferably 70 wt. % or more, and mostpreferably 75 wt. % or more, in each case based on the total weight ofthe material.

Preferably, the total amount of water is in the range of 70 to 99.5 wt.%, more preferably in the range of 75 to 99 wt. %, and most preferablyin the range of 80 to 98 wt. %, in each case based on the total weightof the material.

The total amount of water of an orally consumable material according tothe present invention, in particular of a ready-to-drink compositionaccording to the present invention, is 60 wt. % or more, preferably 70wt. % or more, more preferably 75 wt. % or more, even more preferably 80wt. % or more, in each case based on the total weight of the orallyconsumable material.

Preferably, the total amount of water, preferably of non-deionizedwater, particularly of drinking water or mineral water, of an orallyconsumable material according to the present invention, in particular ofa ready-to-drink composition according to the present invention, is inthe range of from 82 wt. % to 98 wt. %, more preferably in the range offrom 83 wt. % to 96 wt. %, even more preferably in the range of from 84wt. % to 95 wt. %, and most preferably in the range of from 85 wt. % to94 wt. %, in each case based on the total weight of the orallyconsumable material.

In a preferred embodiment, a material according to the present inventioncomprising an above defined (preferred or particularly preferred) totalamount of water has a pH-value at 25° C. of 6.8 or less, preferably inthe range of 1.5 to 6.5, more preferably in the range of 2.0 to 6.0,even more preferably in the range of 2.1 to 5.8, particularly preferablyin the range of 2.2 to 5.0, and most preferably in the range of 2.3 to4.5.

The pH-value of an orally consumable material according to the presentinvention, in particular of a ready-to-drink composition according tothe present invention, when measured at 25° C. (and preferably at 1013mbar) preferably is in the range of from 1.5 to 6.5, preferably in therange of from 1.8 to 6.0, more preferably in the range of from 2.0 to5.5, even more preferably in the range of from 2.0 to 5.0, particularlypreferably in the range of from 2.1 to 4.4, especially preferably in therange of from 2.2 to 4.2, and most preferably in the range of from 2.3to 3.9.

It should be emphasized that the one or more compounds of the aboveformula I, one or more physiologically acceptable salts of a compound ofthe above formula I, or a mixture thereof are stable (preferably attemperatures of 40° C. or lower) for a long period of time (generallymore than 16 weeks at 25° C.) in such aqueous materials at the acidicpH-values indicated hereinbefore, i.e. the compounds of the aboveformula I are not decomposed or degraded to an appreciable orsignificant extent.

In a preferred embodiment, a material according to the present invention(preferably comprising an above defined preferred or particularlypreferred total amount of water and having a pH-value in a preferred orparticularly preferred range indicated above) suitable for oralconsumption, preferably a food or a beverage, comprises

-   -   one or more organic food acids and/or the physiologically        acceptable salt thereof, preferably selected from the group        consisting of acetic acid, adipic acid, caffeotannic acid,        citric acid, iso-citric acid, maleic acid, fumaric acid,        galacturonic acid, glucuronic acid, glyceric acid, glycolic        acid, lactic acid, malic acid, oxalic acid, pyruvic acid, quinic        acid, succinic acid, tannic acid, tartaric acid, and the        physiologically acceptable salts thereof, preferably the sodium        and/or potassium and/or calcium and/or magnesium salts thereof        thereof,        and/or    -   one or more edible inorganic acids and/or the physiologically        acceptable salt thereof, preferably selected from the group        consisting of phosphoric acid, pyrophosphoric acid,        polyphosphoric acids, and bisphosphonic acids (in particular        those explicitly mentioned in paragraph [0050] of US        2010/0151104 A1), and the physiologically acceptable salts        thereof,        and/or    -   one or more high potency sweeteners, preferably selected from        the group consisting of magap, sodium cyclamate, acesulfame K,        neohesperidin dihydrochalcone, saccharin sodium salt, aspartame,        superaspartame, neotame, alitame, sucralose, stevioside,        rebaudiosides (preferably rebaudioside A), lugduname, carrelame,        sucrononate, sucrooctate, monatin, phyllodulcin, hernandulcin,        dihydrochalcone glycosides, glycyrrhizin, glycyrrhetinic acid        and its sweet tasting physiologically acceptable salts,        preferably glycyrrhetinic acid ammonium salt, mogrosides,        liquorice extracts (Glycyrrhizza glabra ssp.), Lippia dulcis        extracts, Momordica ssp. extracts (in particular Momordica        grosvenori [Luo Han Guo]), Hydrangea dulcis extracts and Stevia        ssp. (e.g. Stevia rebaudiana) extracts,    -   preferably one or more high potency sweeteners in a total amount        isosweet to or sweeter than a 1.0 wt. % solution of sucrose in        water, more preferably in a total amount isosweet to or sweeter        than a 2.0 wt. % solution of sucrose in water, even more        preferably in a total amount isosweet to or sweeter than a 3.0        wt. % solution of sucrose in water, particularly preferably in a        total amount isosweet to or sweeter than a 4.0 wt. % solution of        sucrose in water,        and/or    -   one or more sweet tasting mono- or disaccharides, preferably        selected from the group consisting of sucrose, lactose, maltose,        glucose, and fructose, the total amount of said sweet tasting        mono- or disaccharides being in the range of 1.5 to 19 wt. %,        preferably in the range of 2.5 to 16 wt. %, more preferably in        the range of 3.5 to 14 wt. %, particularly preferably in the        range of 4.5 to 13 wt. %, and most preferably in the range of        5.5 to 12 wt. %, in each case based on the total weight of the        material,        and preferably one, two, three, four, five or more flavouring        agents, preferably having a molecular weight in the range of 120        to 300 g/mol, more preferably in the range of 130 to 280 g/mol.

The one or more compounds of formula I and/or the physiologicallyacceptable salts thereof, especially as defined in one of the preferredor particularly preferred embodiments, and the mixtures as defined inone of the preferred or particularly preferred embodiments, allow theprevention of spoilage of materials with such a high proportion of water(and preferably a pH-value at 25° C. in the range of 2.2 to 4.6) bymicroorganisms, within a sealed container for a period of at least 12weeks, preferably at least 16 weeks at 25° C. Thus, a reduction orsubstitution of conventional preservatives (that may pose health and/orenvironmental concerns) is possible.

The one or more compounds of formula I and/or the physiologicallyacceptable salts thereof, especially as defined in one of the preferredor particularly preferred embodiments, and the mixtures as defined inone of the preferred or particularly preferred embodiments, allow to beused together in other known beverage preserving agents in an additiveor synergistic manner to reduce the amount of preservative required andso improve the inventive beverage's sensory impact over beverages havingconventional preservatives. Such other known beverage preserving agentsare preferably selected from the group consisting ofethyl-N-alpha-lauroyl-L-arginate (LAE) and its hydrochloride, dimethyldicarbonate, trans-cinnamic acid, EDTA (ethylene diamine tetraaceticacid) and its physiologically acceptable salts, preferably the sodiumand/or calcium salts thereof, EDDS (ethylene diamine-N,N′-disuccinicacid) and its physiologically acceptable salts, preferably the sodiumand/or calcium salts thereof, polyphosphoric acid and itsphysiologically acceptable salts (preferably comprising or consisting ofsodium hexametaphosphate), bisphosphonic acids and bis-phosphonates (inparticular those explicitly mentioned in paragraph [0050] of US2010/0151104 A1), and the mixtures thereof.

The total amount of ethyl-N-alpha-lauroyl-L-arginate and itshydrochloride preferably is in the range of 1 to 25 ppm, more preferably2 to 12 ppm, based on the total weight of the beverage.

The total amount of dimethyl dicarbonate preferably is in the range of20 to 500 ppm, more preferably 50 to 250 ppm, based on the total weightof the beverage.

The total amount of trans-cinnamic acid preferably is in the range of 1to 40 ppm, more preferably 2 to 30 ppm, based on the total weight of thebeverage.

The total amount of EDTA (ethylene diamine tetraacetic acid) and itsphysiologically acceptable salts is in the range of 0.5 to 50 ppm, morepreferably 1 to 30 ppm, based on the total weight of the beverage.

The total amount of EDDS (ethylene diamine-N,N′-disuccinic acid) and itsphysiologically acceptable salts is in the range of 1 to 500 ppm, morepreferably 20 to 450 ppm, based on the total weight of the beverage.

The total amount of polyphosphoric acid and its physiologicallyacceptable salts is in the range of 10 to 1500 ppm, based on the totalweight of the beverage.

As already mentioned above, the compounds of formula I, preferably thecompounds [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12],[13], [14], [18], [19], [20], [21], and the physiologically acceptablesalts thereof do not exhibit a distinctive taste or unpleasant mouthfeeling, in particular no off-flavours, in particular in the totalamounts used in the ready-to-use product.

The total amount of the compounds of formula I, preferably of thecompounds [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12],[13], [14], [18], [19], [20], [21] and the physiologically acceptablesalts thereof, more preferably of the compounds [1], [4], [5], [6], [7],[8], [9], [10], [12], [13], [14], [18], and the physiologicallyacceptable salts thereof, preferably is in the range of 0.1 to 1000 ppm,more preferably of 0.5 to 500 ppm, particularly preferably of 1 to 250ppm, and most preferably of 2 to 150 ppm, in each case based on thetotal weight of the orally consumable material according to the presentinvention, particularly a food or beverage according to the presentinvention.

Therefore, the compounds of formula I and the physiologically acceptablesalts thereof are preferably used in orally consumable materials,particularly foods or beverages, according to the invention, incombination with one or more flavouring agents, preferably having amolecular weight in the range of 120 to 300 g/mol, more preferably inthe range of 130 to 280 g/mol.

Preferably, one, two, three or more of said flavouring agents are fresh,sweet, fruity, spicy and/or herbal flavouring agents, preferablyselected from the group consisting of menthol (preferably L-menthol,D-menthol, racemic menthol, isomenthol, neoisomenthol, neomenthol),isomenthone, menthone, peppermint oil, L-carvone, D-carvone, spearmintoil, cineol, eucalyptus oil, cinnamaldehyde (preferablytrans-cinnamaldehyde), cinnamic alcohol, cinnamon bark oil, cinnamonleaf oil, methyl cinnamate, benzaldehyde, furfural, furfuryl alcohol,methyl salicylate, wintergreen oil, thyme oil, thymol, carvacrol, cloveoil, camphene, p-cymene, alpha-terpinene, borneol, eugenol, anise oil,star anise oil, anethole (preferably trans-anethole), anisole,cis-3-hexenol, cis-3-hexenyl acetate, D-limonene, L-limonene, linalool,citral, geraniol, geranyl acetate, nerol, citronellol, citronellal,alpha-phellandrene, beta-phellandrene, alpha-pinene, beta-pinene,vanilla extract, vanillin, ethylvanillin,2-hydroxy-4-methoxybenzaldehyde, 2,5-dimethyl-4-hydroxy-3(2H)-furanone,2-ethyl-4-hydroxy-5-methyl-3(2H)-furanone,2-ethyl-5-methyl-4-hydroxy-3(2H)-furanone,5-ethyl-2-methyl-4-hydroxy-3(2H)-furanone,3-hydroxy-4,5-dimethyl-2(5H)-furanone, maltol, ethylmaltol, coumarin,butyrolactone, gamma-undecalactone, gamma-nonalactone,4-methyl-delta-lactone, massoia lactone, sotolon, delta-decalactone,tuberolactone, methyl sorbate, 2-hydroxy-3-methyl-2-cyclopentenones,n-butyl acetate, isoamyl acetate, ethyl butyrate, n-butyl butyrate,isoamyl butyrate, ethyl 3-methyl-butyrate, ethyl n-hexanoate, allyln-hexanoate, n-butyl n-hexanoate, ethyl n-octanoate,ethyl-3-methyl-3-phenylglycidate, ethyl-2-trans-4-cis-decadienoate,4-(p-hydroxyphenyl)-2-butanone, 1,1-dimethoxy-2,2,5-trimethyl-4-hexane,2,6-dimethyl-5-hepten-1-al, and phenylacetaldehyde.

Preferably, one, two, three or more of said flavouring agents are sweet,fruity and/or spicy flavouring agents, preferably selected from thegroup consisting of trans-cinnamaldehyde, cinnamic alcohol, methylcinnamate, benzaldehyde, furfural, furfuryl alcohol, camphene, p-cymene,alpha-terpinene, borneol, eugenol, trans-anethole, anisole,cis-3-hexenol, cis-3-hexenyl acetate, D-limonene, L-limonene, linalool,citral, geraniol, geranyl acetate, nerol, citronellol, citronellal,alpha-phellandrene, beta-phellandrene, alpha-pinene, beta-pinene,vanilla extract, vanillin, ethylvanillin,2-hydroxy-4-methoxybenzaldehyde, 2,5-dimethyl-4-hydroxy-3(2H)-furanone,2-ethyl-4-hydroxy-5-methyl-3(2H)-furanone,2-ethyl-5-methyl-4-hydroxy-3(2H)-furanone,5-ethyl-2-methyl-4-hydroxy-3(2H)-furanone,3-hydroxy-4,5-dimethyl-2(5H)-furanone, maltol, ethylmaltol, coumarin,gamma-undecalactone, gamma-nonalactone, 4-methyl-delta-lactone, massoialactone, sotolon, delta-decalactone, tuberolactone, methyl sorbate,n-butyl acetate, isoamyl acetate, ethyl butyrate, n-butyl butyrate,isoamyl butyrate, ethyl 3-methyl-butyrate, ethyl n-hexanoate, allyln-hexanoate, n-butyl n-hexanoate, ethyl n-octanoate,ethyl-3-methyl-3-phenylglycidate, ethyl-2-trans-4-cis-decadienoate,4-(p-hydroxyphenyl)-2-butanone, 2,6-dimethyl-5-hepten-1-al, andphenylacetaldehyde.

The present invention also relates to foods, such as meat, meatproducts, fish and seafood products, with an increased shelf lifestability and an increased resistance against the growth ofGram-positive bacteria. The preparation process for manufacturingfoodstuffs using the compounds of formula I and/or the physiologicallyacceptable salts thereof according to the invention comprises, forexample, combining an uncooked meat, meat products, fish or seafoodproduct with one or more phosphates, one or more lactates, lactic acid,and preferably further and/or a flavouring agent, followed by furtherprocessing such as packing or cooking. In this specific aspect, thepresent invention makes use of phosphates which are functional inprotein activation of meat, meat products, fish or seafood and have alsoproperties to absorb lactates and flavouring agents.

In this context the present invention relates to a foodstuff treatmentcomposition, particularly for the treatment of meat, meat products, fishand seafood products, said composition comprising (i) one or morecompounds of formula I and/or the physiologically acceptable saltsthereof, (ii) lactic acid and/or lactates, and (iii) one or morephosphates.

In a preferred embodiment of the invention said foodstuff treatmentcomposition comprises

(i) one, two, three or more of compounds [1], [2], [3], [4], [5], [6],[7], [8], [9], [10], [11], [12], [13], [14], [18], [19], [20], [21]and/or the physiologically acceptable salts thereof, preferably in atotal amount of 0.0001 to 1 wt. %, more preferably in a total amount of0.0005 to 0.5 wt. %, even more preferably in a total amount of 0.001 to0.1 wt. %, particularly preferably in a total amount of 25 to 500 ppm,(ii) sodium lactate and/or potassium lactate, preferably in a totalamount of 0.5 to 25 wt. %, more preferably in a total amount of 1 to 20wt. %, even more preferably in a total amount of 1.5 to 15 wt. %,(iii) one or more sodium and/or potassium phosphates selected from thegroup consisting of sodium and/or potassium orthophosphates,pyrophosphates (diphosphates), metaphosphates, and polyphosphates(hexametaphosphates), preferably in a total amount of 1 to 45 wt. %,more preferably in a total amount of 2 to 30 wt. %, even more preferablyin a total amount of 3 to 25 wt. %,(iv) preferably water, more preferably water in a total amount of 50 wt.% or more, even more preferably in a total amount of 60 wt. % or more,and optionally(v) one or more further constituents selected from the group consistingof sodium chloride, sodium nitrite, potassium nitrite, sodium nitrate,potassium nitrate, calcium lactate, sodium diacetate, acetic acid,sodium acetate, sodium diacetate, potassium acetate, potassium diacetatecitric acid, and sodium citrate,wherein the amounts in each case are based on the total weight of thefoodstuff treatment composition.

In another preferred embodiment of the invention the one or more sodiumand/or potassium phosphate salts of constituent (iii) are selected fromtrisodium phosphate (Na₃PO₄), tetrasodium pyrophosphate (Na₄P₂O₇),sodium tripolyphosphate (Na₅P₃O₁₀), tripotassium phosphate (K₃PO₄),tetrapotassium pyrophosphate (K₄P₂O₇), potassium tripolyphosphate(K₅P₃O₁₀), and sodium hexametaphosphate (NaPO₃)₆.

These foodstuff treatment compositions are particularly useful for thetreatment of meat, meat products, fish and seafood products, to increasethe resistance of the foodstuff against the growth of bacteria, inparticular of the genera Listeria (particularly Listeria monocytogenes),Lactobacillus, Clostridia, Micrococcus (particularly Micrococcusluteus), and/or Bacillus (particularly Bacillus cereus), whereby thefoodstuff treatment composition is applied to the food in an amount toachieve a total amount of 0.25 to 6 wt %, preferably of 0.5 to 4 wt. %,of constituents (ii) lactic acid and lactates and (iii) phosphates inthe final treated foodstuff.

In a preferred embodiment, a material according to the present invention(preferably comprising an above defined preferred or particularlypreferred total amount of water and having a pH-value in a preferred orparticularly preferred range indicated above) is a cosmetic productsuitable for topical application onto the mucous membrane (mucosa)and/or the epidermis of a mammal, preferably in the form of anO/W-lotion, a milk, a (hydro)gel, a body care and/or hair care product(such as preferably a shower gel and/or a shampoo, a hair conditioningproduct, or a deodorant), comprises

-   -   one or more surfactants not corresponding to formula I as        defined in the context of the present invention, preferably one        or more surfactants selected from the group consisting of        anionic tensides, cationic tensides, non-ionic tensides,        amphoteric (zwitterionic) tensides, and biosurfactants,        and/or    -   one or more mono-, di- or triols having 2 to 14 carbon atoms,        preferably one or more di- or triols having 3 to 12 carbon        atoms, wherein preferably the total amount of mono-, di- and        triols is 1 wt. % or more, more preferably in the range of 1.1        to 30 wt. %,        and/or    -   one or more fragrance substances, preferably a mixture of three,        five, eigh for more fragrance substances, more preferably a        perfume, preferably fragrance substances in a total amount of        0.1 to 3 wt. %, more preferably in a total amount of 0.15 to 2        wt. %, even more preferably in a total amount of 0.2 to 1 wt. %,        wherein the percentages in each case are based on the total        weight of the cosmetic product.

Preferably one, several or all mono-, di- or triols having 2 to 14carbon atoms are selected from the group consisting of ethanol,1-propanol, 2-propanol, ethylene glycol, 1,2-propylene glycol, glycerol(glycerin), 1,3-propandiol, 2-methyl-1,3-propandiol, trimethylolpropane,1,2-butandiol, 1,3-butandiol, 1,4-butandiol, 1,2,3-butantriol,1,2,4-butantriol, 1-pentanol, 2-pentanol, 3-pentanol, 1,2-pentandiol,1,3-pentandiol, 1,5-pentandiol, 1-hexanol, 2-hexanol, 3-hexanol,1,2-hexandiol, 1,3-hexandiol, dipropylene glycol, 1-octanol, 2-octanol,3-octanol, 1,2-octandiol (caprylyl glycol), 1,3-octandiol,2-methyl-5-cyclohexylpentanol, 2-methyl-4-phenyl-2-butanol,4-methyl-4-phenyl-2-pentanol (dimethyl phenyl 2-butanol), 1-decanol,2-decanol, 1,2-decandiol, 3-(2-ethylhexyloxy)propane-1,2-diol(ethylhexylglycerin, octoxyglycerin), 1-dodecanol, 2-dodecanol,1,2-dodecandiol, 1,12-dodecandiol, 1-tetradecanol, 2-tetradecanol,1,2-tetradecandiol and 1,14-tetradecandiol, wherein preferably the totalamount of mono-, di- and triols having 2 to 14 carbon atoms is 0.5 wt. %or more, more preferably 1.0 wt. % or more, even more preferably 1.25wt. % or more, and preferably is in the range of 1.25 to 25 wt. %,particularly in the range of 1.5 to 20 wt. %, in each case based on thetotal weight of the cosmetic product.

Preferably one, several or all di- or triols having 3 to 12 carbon atomsare selected from the group consisting of 1,2-propylene glycol, glycerol(glycerin), 1,3-propandiol, 2-methyl-1,3-propandiol, trimethylolpropane(2-(hydroxymethyl)-2-ethylpropane-1,3-diol), 1,2-butandiol,1,4-butandiol, 1-pentanol, 2-pentanol, 1,2-pentandiol, 1,5-pentandiol,1-hexanol, 2-hexanol, 1,2-hexandiol, dipropylene glycol, 1-octanol,2-octanol, 1,2-octandiol, 2-methyl-4-phenyl-2-butanol,4-methyl-4-phenyl-2-pentanol, 1-decanol, 1,2-decandiol, 1-dodecanol,1,2-dodecandiol, 1,12-dodecandiol, and3-(2-ethylhexyloxy)propane-1,2-diol (ethylhexylglycerin), whereinpreferably the total amount of di- and triols having 3 to 12 carbonatoms is 0.5 wt. % or more, more preferably 1.0 wt. % or more, even morepreferably is in the range of 1.25 to 15 wt. %, particularly in therange of 1.5 to 10 wt. %, in each case based on the total weight of thecosmetic product.

The anionic tensides, cationic tensides non-ionic tensides, amphoteric(zwitterionic) tensides, and biosurfactants are preferably selected from

-   -   anionic tensides based on permanent anions (sulfate, sulfonate,        phosphate) or pH-dependent anions (carboxylate), preferably        sulfates [alkyl sulfates, such as ammonium lauryl sulfate,        sodium lauryl sulfate (SDS, sodium dodecyl sulfate), alkyl ether        sulfates, such as sodium laureth sulfate, also known as sodium        lauryl ether sulfate (SLES), sodium myreth sulfate], sulfonates        [docusates, such as dioctyl sodium sulfosuccinate, sulfonate        fluorosurfactants (perfluorooctanesulfonate (PFOS),        perfluorobutanesulfonate), alkyl benzene sulfonates], phosphates        [alkyl aryl ether phosphate, alkyl ether phosphate],        carboxylates [alkyl carboxylates, fatty acid salts (soaps), such        as sodium stearate, sodium lauroyl sarcosinate, carboxylate        fluorosurfactants, such as perfluorononanoate,        perfluorooctanoate (PFOA or PFO)],    -   cationic tensides based on pH-dependent primary, secondary, or        tertiary amines (such as octenidine dihydrochloride, quaternary        ammonium cations, preferably alkyltrimethylammonium salts (such        as cetyl trimethylammonium bromide (hexadecyl trimethyl ammonium        bromide), cetyl trimethylammonium chloride, cetylpyridinium        chloride, benzalkonium chloride, benzethonium chloride,        dimethyldioctadecylammonium chloride and        dioctadecyldimethylammonium bromide),    -   zwitterionic (amphoteric) tensides based on primary, secondary,        or tertiary amines or quaternary ammonium cation with sulfonates        (such as        (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate)        (CHAPS), sultaines (such as cocamidopropyl hydroxysultaine),        carboxylates (e.g. from amino acids, imino acids), betaines        (such as cocamidopropyl betaine), and phosphates (such as        lecithins),    -   nonionic tensides, preferably fatty alcohols (such as cetyl        alcohol, stearyl alcohol, cetostearyl alcohol (essentially        consisting of cetyl and stearyl alcohols), oleyl alcohol),        polyoxyethylene glycol alkyl ethers        CH₃—(CH₂)₁₀₋₁₆—(O—C₂H₄)₁₋₂₅—OH (such as octaethylene glycol        monododecyl ether, pentaethylene glycol monododecyl ether),        polyoxypropylene glycol alkyl ethers        CH₃—(CH₂)₁₀₋₁₆—(O—C₃H₆)₁₋₂₅—OH, glucoside alkyl ethers        CH₃—(CH₂)₁₀₋₁₆—(O-glucoside)₁₋₃-OH (such as decyl glucoside,        lauryl glucoside, octyl glucoside), polyoxyethylene glycol        octylphenol ethers C₈H₁₇—(C₆H₄)—(O—C₂H₄)₁₋₂₅—OH (such as Triton        X-100), polyoxyethylene glycol alkylphenol ethers        C₉H₁₉—(C₆H₄)—(O—C₂H₄)₁₋₂₅—OH (such as nonoxynol-9), glycerol        alkyl esters (such as glyceryl laurate), polyoxyethylene glycol        sorbitan alkyl esters (such as polysorbates, preferably        polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65,        polysorbate 80, polysorbate 85 and/or polysorbate 120; these are        all commercially available, e.g. under the brand names Canarcel®        or Tween®), sorbitan alkyl esters, cocamide MEA, cocamide DEA,        dodecyldimethylamine oxide, block copolymers of polyethylene        glycol and polypropylene glycol (such as poloxamers        (commercially available, e.g. under the brand name Pluronic®)),        and polyethoxylated tallow amine (POEA),    -   biosurfactants, preferably sophoroplipids, rhamnolipids,        mannosyl-erythritol lipids, and lipopeptides (preferred        lipopeptides are chlamydocin, surfactin, lichenysin G, and        fengycin-like lipopeptides).

Preferably, one, two, three, four, five or more fragrance substanceswith one or more notes selected from the group fresh, floral (flowery),aldehydic, watery, fruity, sweet, woody, musky, green and herbal, morepreferably with one or more notes selected from the group floral(preferably rose and/or lily-of-the-valley (muguet)), aldehydic,vanilla, citrus, sandalwood, and musk.

The epidermis refers to the outermost layers of cells in the skin of amammal, in particular certain parts of the body of a human being, namelyhand, arm, foot, head and axillary region (particularly the armpit). Themucous membrane (mucosa) lines cavities that are exposed to the externalenvironment and internal organs, particularly at the nostrils, the mouth(oral cavity), the lips, the eyelids, and the genital area.

A cosmetic deodorant composition according to the present inventionpreferably comprises

-   -   an antimicrobial effective amount of one or more compounds of        formula I and/or the physiologically acceptable salts thereof,        preferably 2 ppm or more, more preferably 5 ppm or more, even        more preferably 10 ppm or more,    -   water, preferably in a total amount of 10 wt. % or more, more        preferably in a total amount of 50 wt. % or more, particularly        preferably in a total amount of 60 wt. % or more,    -   one or more alcohols selected from the group consisting of        ethanol, 1,2-propylene glycol, glycerol (glycerin),        2-methyl-1,3-propandiol, 1,2-butandiol, 1,3-butandiol        1,4-butandiol, 1,2,4-butantriol, 1-pentanol, 1,2-pentandiol,        1,5-pentandiol, 1,2-hexandiol, 1-octanol, 1,2-octandiol, and        3-(2-ethylhexyloxy)propane-1,2-diol (ethylhexylglycerin,        octoxyglycerin), preferably in a total amount of 1.5 wt. % or        more, more preferably in a total amount of 2.5 wt. % or more,        wherein the amounts indicated in each case relate to the total        weight of the cosmetic deodorant composition.

Such a cosmetic deodorant composition according to the present inventionpreferably additionally comprises one or more constituents selected fromthe group consisting of antiperspirants, fragrance substances, andfurther surfactants.

Antiperspirants inhibit the secretion of sweat. As antiperspirantsastringent metal salts are generally used, in particular inorganic andorganic metal salts of the elements aluminum, zinc, magnesium, tin andzirconium as well as mixtures thereof are used. Frequently, aluminum andzirconium salts and their mixtures are also used in complex form, withpropylene glycol, polyethylene glycol or glycerin being used ascomplexing agents. One ore more antiperspirants are preferably selectedfrom the group consisting of aluminium chlorohydrate; aluminiumsesquichlorohydrate, aluminium chlorohydrex propylene glycol, aluminiumdichlorohydrex propylene glycol, aluminium sesquichlorohydrex propyleneglycol, aluminium chlorohydrex polyethylene glycol, aluminiumdichlorohydrex polyethylene glycol, aluminium sesquichlorohydrexpolyethylene glycol, aluminium chloride, aluminium zirconiumchlorohydrate, aluminium zirconium trichlorohydrate, aluminium zirconiumtetrachlorohydrate, aluminium zirconium pentachlorohydrate, aluminiumzirconium octachlorohydrate, aluminium zirconiumtrichlorohydrex-glycerin, aluminium zirconiumtetrachlorohydrex-glycerin, aluminium zirconiumpentachlorohydrex-glycerin, aluminium zirconiumoctachlorohydrex-glycerin, basic aluminium chloride, zirconiumhydroxychloride, zirconium chloride.

Preferably one or more of the further surfactants are selected from thegroup consisting of anionic tensides, cationic tensides, non-ionictensides, or amphoteric tensides explicitly mentioned above.

Examples of preferred materials according to the present invention,particularly orally consumable materials, are

-   -   fruit or vegetable containing products (preferably products        containing juice, extract, puree, mash, pulp, concentrate, dried        parts of lemon, lime, grapefruit, orange, sweet orange, bitter        orange, bergamot, mandarin, apple, pear, prickly pear, peach,        apricot, fig, pineapple, prune, mango, melon, plum, kiwi,        lychee, banana, cherry, sweet cherry, strawberry, raspberry, red        currant, black currant, blackberry, blueberry, marionberry,        passion fruit, grapes (white grape, red grape, green grape,        purple grape), pomegranate, acerola, tomato, carrot, parsnip,        pumpkin, lettuce, cabbage, fermeted cabbage, bean, pea, potato,        bell pepper, red chilli, green chilli, onion, celery, cucumber,        leek, broccoli, cauliflower, radish, aubergine, zucchini),    -   soy based products (preferably soy milk, soy drinks, soy        yoghurts),    -   non-alcoholic beverages and syrups (preferably lemonades,        beverage concentrates (syrups), non-carbonated soft drinks, and        carbonated soft drinks),    -   alcoholic beverages,    -   products containing 50 wt. % or more of water and one or more        other extracts from herbs and/or spices (preferably selected        from the group consisting of vanilla, cinnamon, anise, fennel,        clove, cardamom, tamarind, nutmeg, allspice, black pepper,        licorice, ginger, rose hip, green tea, red tea, rooibos tea,        mate tea, honeybush tea, pu-erh tea, oolong tea, black tea,        coffee bean, cocoa bean, peppermint, spearmint, and        wintergreen),    -   non-frozen fermented or non-fermented dairy or dairy-based        products (preferably milk, quark, cream cheese, cheese,        custards, puddings, mousses, milk based drinks, drink yoghurts,        and yoghurts),    -   frozen products (preferably ice-cream, frozen yoghurt, sorbet,        ice milk, frozen custard, water-ices, granitas, sherbets. and        frozen fruit purees),    -   doughs and batters (preferably pancake batter, wafle dough, cake        doughs, bread dough, bun dough, pasta doughs),    -   O/W-emulsions (spreads, sauces, and (salad) dressings).

In a preferred embodiment, the one or more compounds of formula I and/orthe physiologically acceptable salts thereof (for use) according to thepresent invention, the extracts according to the present invention arecombined with one or more ingredients selected from the group consistingof lactic acid, lactose, sucrose, calcium salts (preferably calciumphosphate, calcium gluconate, calcium lactate, and calcium chloride),calcium oxide, magnesium salts, magnesium oxide, iron salts (preferablyferrous fumarate, ferrous succinate, iron sucrate-malate, ironfructate-malate, iron sucrate-citrate, iron fructatecitrate, ironsucrate-ascorbate, iron fructate-ascorbate, and mixtures thereof),vitamin A (particularly retinol (vitamin A1)), vitamin B6, vitamin B12,vitamin C, vitamin D, vitamin E, thiamine, niacin, biotin, riboflavin,pantothenic acid, phytic acid, daidzein, genistein, proteins (preferablycasein, caseinates (preferably sodium caseinate), milk protein, milkprotein hydrolyzate, milk protein isolate, whey protein, whey proteinhydrolyzate, whey protein isolate, soy protein, soy protein hydrolyzate,soybean protein isolate), milk powder, soy powder, polyunsaturated fattyacids [preferably omega-3-, omega-6- and/or omega-9-fatty acids,preferably selected from the group consisting of docosahexaenoic acid(DHA, all-cis-docosa-4,7,10,13,16,19-hexaenoic acid), eicosatetraenoicacid (ETA, all-cis-8,11,14,17-eicosatetraenoic acid), eicosatetraenoicacid (ETA, all-cis-8,11,14,17-eicosatetraenoic acid), stearidonic acid(SDA, all-cis-6,9,12,15-octadecatetraenoic acid), docosapentaenoic acid(DPA; clupanodonic acid, all-cis-7,10,13,16,19-docosapentaenoic acid),linoleic acid, α-linolenic acid (all-cis-9,12,15-octadecatrienoic acid),and γ-linolenic acid], soy oil, butterfat, (refined) fish oil, algaloil, squid oil, flaxseed oil, grape seed oil, and triglycerides derivedfrom the fatty acids myristic acid, palmitic acid and/or oleic acid,thereby forming preferred materials according to the present invention,particularly materials suitable for oral consumption.

Preferably, a material according to the present invention (preferablycomprising an above defined preferred or particularly preferred totalamount of water and having a pH-value in a preferred or particularlypreferred range indicated above) suitable for oral consumption comprisesa total amount of glutamic acid and sodium glutamate of less than 0.2wt. %, preferably of less than 0.15 wt. %, more preferably of less than0.1 wt. %, particularly preferably of less than 0.05 wt. %, and mostpreferably is free of glutamic acid and sodium glutamate.

Examples of stabilizers and/or thickeners which may be part of a(preferably orally consumable) material according to the presentinvention are preferably selected from the group consisting ofcarbohydrate polymers (polysaccharides, preferably starches,polydextrose (E-number E1200), physically modified starches, chemicallymodified starches (preferably oxidized starch (E-number E1404),monostarch phosphate (E-number E1410), distarch phosphate (E-numberE1412), phosphated distarch phosphate (E-number E1413), acetylateddistarch phosphate (E-number E1414), acetylated starch (starch acetateesterified with acetic anhydride; E-number E1420), acetylated distarchadipate (E-number E1422), hydroxy propyl starch (E-number E1440),hydroxy propyl distarch phosphate (E-number E1442) starch sodium octenylsuccinate (E-number E1450), and acetylated oxidized starch (E-numberE1451)), cyclodextrins, celluloses, modified celluloses (preferablymethylcellulose, ethylcellulose, hydroxymethyl cellulose, hydroxyethylcellulose, hydroxypropyl cellulose, hydroxyethyl methylcellulose,hydroxypropyl methylcellulose), gum Arabic (gum acacia), gum ghatti, gumtragacanth, gum karaya, carrageenan, guar gum, carob gum (carob flour,locust bean gum, E-number E410), alginates, pectins, inulin and xanthangum.

In a further preferred embodiment the total amount of compounds offormula I and the physiologically acceptable salts thereof in an orallyconsumable material according to the present invention, in particular ofa ready-to-drink composition according to the present invention, is inthe range of from 1 to 200 ppm, more preferably in the range of from 2to 150 ppm, even more preferably in the range of from 5 to 100 ppm, ineach case based on the total weight of the orally consumable material.

Preferably, the total amount of glucose, fructose and sucrose of anorally consumable material according to the present invention, inparticular of a ready-to-drink composition according to the presentinvention, is in the range of from 1.5 to 15.0 wt. %, more preferably inthe range of from 2.0 to 12.0 wt. %, even more preferably in the rangeof from 2.5 to 10.5 wt. %, particularly preferably in the range of from3.0 to 9.5 wt. %, in each case based on the total weight of the orallyconsumable material.

Glucose, fructose and sucrose are commercially readily available fromvarious sources and in various forms, and may be obtained from suitableplant sources, for example from sugar beet (Beta vulgaris ssp., sugarfractions, sugar syrup, molasses), from sugar cane (Saccharumofficinarum ssp., e.g. molasses, sugar syrups), from sugar maple (Acerssp.), from agave (agave thick juice), sorghum, certain palm trees,invert sugar syrup, high fructose corn syrup (HFCS, also calledglucose-fructose syrup, e.g. made from wheat or corn starch), or fruitconcentrates (e.g. from apples or pears, apple syrup, pear syrup).

In a preferred embodiment, an orally consumable material according tothe present invention, in particular a ready-to-drink compositionaccording to the present invention, preferably comprises one, two, threeor more fruity flavouring agents having a molecular weight in the rangeof 135 to 190 g/mol, more preferably a molecular weight in the range of135 to 180 g/mol, said fruity flavouring agents preferably imparting aflavour note selected from the group consisting of lemon, lime,grapefruit, orange, sweet orange, bitter orange, bergamot, mandarin,apple, pear, prickly pear, peach, apricot, pineapple, prune, mango,melon, plum, kiwi, lychee, banana, cherry, sweet cherry, strawberry,raspberry, red currant, black currant, blackberry, blueberry, passionfruit, grape, pomegranate, acerola, coconut, vanilla and mixturesthereof.

Preferably, an orally consumable material according to the presentinvention, in particular of a ready-to-drink composition according tothe present invention, comprises one or more organic food acids (i.e.organic acids suitable for oral consumption), preferably selected fromthe group consisting of acetic acid, adipic acid, caffeotannic acid,citric acid, iso-citric acid, maleic acid, fumaric acid, galacturonicacid, glucuronic acid, glyceric acid, glycolic acid, lactic acid, malicacid, oxalic acid, pyruvic acid, quinic acid, succinic acid, tannicacid, tartaric acid, and the physiologically acceptable salts thereof,preferably the sodium and/or potassium and/or calcium and/or magnesiumsalts thereof.

Preferred physiologically acceptable salts of phosphoric acid are forexample sodium acetate, monosodium phosphate, disodium phosphate,monopotassium phosphate, dipotassium phosphate, sodiumhexametaphosphate, and sodium bis-phosphonates.

Preferably, an orally consumable material according to the presentinvention, in particular a ready-to-drink composition according to thepresent invention, comprises one or more acids selected from the groupconsisting of citric acid, tartaric acid, lactic acid, malic acid,maleic acid, fumaric acid, phosphoric acid, pyrophosphoric acids,polyphosphoric acids, bisphosphonic acids and the physiologicallyacceptable salts thereof.

A more preferred orally consumable material according to the presentinvention, in particular a ready-to-drink composition according to thepresent invention, comprises

-   -   sucrose, and/or    -   a mixture of glucose and fructose, wherein the amount of        fructose is in the range of from 30 to 95 wt. %, preferably 40        to 92 wt. %, based on the total amount of glucose and fructose        in the orally consumable material.

Another preferred orally consumable material according to the presentinvention, in particular a ready-to-drink composition according to thepresent invention, comprises one or more further constituents suitablefor consumption selected from:

-   -   one or more emulsifiers, and/or    -   one or more antioxidants and optionally one or more substances        for intensifying the antioxidative effect of said antioxidants,        and/or    -   one or more preservatives, and/or    -   one or more vitamins and the physiologically acceptable salts or        esters thereof, and/or    -   one or more coloring agents, and/or    -   one or more weighting agents, and/or    -   one or more sugar alcohols, and/or    -   one or more high potency sweeteners, preferably one or more        naturally occurring high potency sweeteners, and/or    -   one or more stabilizers and/or thickeners.

Preferably, an orally consumable material according to the presentinvention, in particular a ready-to-drink composition according to thepresent invention, comprises one or more further constituents suitablefor oral consumption, particularly

-   -   one or more emulsifiers, preferably selected from the group        consisting of lecithins (preferably naturally occurring        lecithins, particularly lecithin from egg or soy), phospholipids        (preferably phosphatidylcholines), monoacylglycerols, and        diacylglycerols,        and/or    -   one or more antioxidants and optionally one or more substances        for intensifying the antioxidative effect of said antioxidants,        and/or    -   one or more preservatives (preferably selected from the group        consisting of benzoic acid, sodium benzoate, potassium benzoate,        sorbic acid, sodium sorbate, sodium sorbate, butylated        hydroxyanisole (BHA), and butylated hydroxytoluene (BHT)),        preferably in a total amount of from 0.05 to 0.5 wt. %, more        preferably of from 0.1 to 0.3 wt. %, based on the total weight        of the composition,        and/or    -   one or more vitamins and the physiologically acceptable salts or        esters thereof, preferably selected from the group consisting of        vitamin A, vitamin A palmitate, vitamin B1, vitamin B2        (riboflavin), vitamin B3 (niacin), vitamin B6, vitamin B9 (folic        acid) vitamin B12, vitamin C (ascorbic acid), monosodium        ascorbate, monopotassium ascorbate, calcium diascorbate,        magnesium diascorbate, ascorbyl palmitate, ascorbyl stearate,        vitamin D, and vitamin E, vitamin E acetate, vitamin E        palmitate, vitamin H (biotin), vitamin K,        and/or    -   one or more coloring agents, preferably selected form the group        consisting of carotenes (E-number E160a, preferably        beta-carotene), paprika extract (E-number E160c), red beet juice        powder (comprising betanine, beetroot red, E-number E162),        annatto (E-number E160b), anthocyanins (E-number E163),        chlorophylls (E-number E140), turmeric (E-number E100,        comprising curcumin), tartrazine (FD&C Yellow No. 5, E-number        E102), amaranth (E-number E123), titanium dioxide (E-number        E171), iron oxides and iron hydroxides (E-number E172),        erythrosine (E-number E127), caramel color (E-number E150,        preferably E150d), FD&C yellow No. 6 (E-number E110), allura red        (FD&C red No. 40, E-number E129), FD&C green No. 3 (fast green,        E-number E143), FD&C blue No. 1 (brilliant blue, E-number E133)        and FD&C blue No. 2 (indigotine, E-number E132),        and/or    -   one or more bitter tasting substances selected from the group        consisting of quinine, neohesperidin, hesperidin, naringin,        quercitrin, phloridzin, phloretin-2-O′-xyloglucoside, caffeic        acid, chlorogenic acid, neochlorogenic acid, cryptochlorogenic        acid, limonoids (preferably limonin or nomilin from citrus        fruits), lupolones from hops, humulones from hops, gallic and        ellagic acid esters of carbohydrates (preferably        pentagalloylglucose), catechins and epicatechins (preferably        selected from the group consisting of galloylated catechins,        galloylated epicatechins, gallocatechins or epigallocatechins,        galloylated gallocatechins or galloylated epigallocatechins),        theaflavins (in particular theaflavin, isotheaflavin,        neotheaflavin), galloylated theaflavins, and procyanidines        (=proanthocyanidines) (in particular Procyanidin B1, Procyanidin        B2, Procyanidin A2, Procyanidin B5, and Procyanidin C1),        and/or    -   one or more stabilizers and/or thickeners, preferably selected        from the group consisting of sodium octenyl succinate,        carboxymethyl cellulose, maltodextrin, gum Arabic, guar gum,        carob gum, alginates, pectin, and xanthan gum.

Examples of stabilizers and/or thickeners which may be part of an orallyconsumable material according to the present invention, in particular ofa ready-to-drink composition according to the invention, are preferablyselected from the group consisting of carbohydrate polymers(polysaccharides), cyclodextrins, starches, degraded starches (starchhydrolysates), chemically or physically modified starches (preferablystarch sodium octenyl succinate, E1450), modified celluloses (preferablycarboxymethyl cellulose), gum Arabic (gum acacia), gum ghatti, gumtragacanth, gum karaya, carrageenan, guar gum, carob gum (carob flour),alginates, pectin, inulin and xanthan gum.

If an orally consumable material according to the present invention, inparticular a ready-to-drink composition according to the presentinvention, comprises one or more thickeners, then the total amount ofthickeners preferably is in the range of from 0.0025 to 1 wt. %, morepreferably in the range of from 0.01 to 0.4. %, even more preferably inthe range of from 0.015 to 0.2. %, in each case based on the totalweight of the composition.

An orally consumable material according to the present invention, inparticular a ready-to-drink composition according to the presentinvention, preferably comprises 200 ppm or more hydrogen carbonate (HCO₃⁻), more preferably 250 ppm or more hydrogen carbonate, even morepreferably 300 ppm or more hydrogen carbonate, and particularlypreferably 400 ppm or more hydrogen carbonate, in each case based on thetotal weight of the orally consumable material.

If an orally consumable material according to the present invention, inparticular a ready-to-drink composition according to the presentinvention, is carbonated, the total amount of carbon dioxide (CO₂)preferably is in the range of from 0.02 to 5.0 wt. %, more preferably inthe range of from 0.05 to 3 wt. %, even more preferably in the range offrom 0.1 to 2.5 wt. %, particularly preferably in the range of from 0.2to 2.0 wt. %, most preferably in the range of from 0.25 to 1.5 wt. %, ineach case based on the total weight of the orally consumable material.

An orally consumable material according to the present invention, inparticular a ready-to-drink composition according to the presentinvention, may additionally comprise lactose and/or maltose, and/or oneor more sugar alcohols such as dulicitol, fucitol, maltitol, erythritol,isomaltitol (E 953), lactitol (E 966), maltitol, mannitol (E421),sorbitol (E420), xylitol (E967), and mixtures thereof.

An orally consumable material according to the present invention, inparticular a ready-to-drink composition according to the presentinvention, may additionally comprise one or more high potency sweetenersare preferably selected from the group consisting of sodium cyclamate,acesulfame K, neohesperidin dihydrochalcone, saccharin, saccharin sodiumsalt, aspartame, superaspartame, neotame, alitame, sucralose, magap,lugduname, carrelame, sucrononate, sucrooctate, miraculin, curculin,monellin, mabinlin, thaumatin, curculin, brazzein, pentadin, or extractsor fractions thereof obtained from natural sources containing said aminoacids and/or proteins, neohesperidin dihydrochalcone, steviolgylcoside,stevioside, steviolbioside, rebaudiosides (preferably rebaudioside A,rebaudioside B, rebaudioside C, rebaudioside D, rebaudioside E,rebaudioside F, rebaudioside G, rebaudioside H, dulcoside, rubusoside),suavioside A, suavioside B, suavioside G, suavioside H, suavioside I,suavioside J, baiyunoside 1, baiyunoside 2, phlomisoside 1, phlomisoside2, phlomisoside 3, phlomisoside 4, abrusoside A, abrusoside B,abrusoside C, abrusoside D, cyclocaryoside A and cyclocaryoside I,oslandin, polypodoside A, strogin 1, strogin 2, strogin 4, selligueaninA, dihydroquercetin-3-acetate, perillartine, telosmoside A₁₅, periandrinI-V, pterocaryoside, cyclocaryoside, mukurozioside, bryoside,bryonoside, bryonodulcoside, carnosifloside, scandenoside, gypenoside,trilobtain, phloridzin, dihydroflavanol, hematoxylin, cyanin,chlorogenic acid, albiziasaponin, telosmoside, gaudichaudioside,mogroside, hernandulcine, monatin, glycyrrhetin acid, glycyrrhizin,phyllodulcin, or the physiologically acceptable salts thereof,preferably the respective potassium, sodium, calcium or ammonium saltsthereof, liquorice extracts (Glycyrrhizza glabra ssp.), Lippia dulcisextracts, Momordica ssp. extracts or individual substances (inparticular Momordica grosvenori [Luo Han Guo] and the mogrosidesobtained therefrom), Hydrangea dulcis or Stevia ssp. (e.g. Steviarebaudiana) extracts or individual substances.

An orally consumable material according to the present invention, inparticular a ready-to-drink composition according to the presentinvention, preferably comprises one or more high potency sweeteners,preferably selected from the group indicated above, more preferablyselected from the group consisting of aspartame, neotame,superaspartame, advantame, saccharin, sucralose, cyclamate, acesulfam,tagatose, monellin, stevioside, rebaudioside A, rebaudioside C,rebaudioside D, rubusosid, phyllodulcin, hernandulcin, thaumatin,brazzein, miraculin, glycyrrhizin, glycyrrhetinic acid, thephysiologically acceptable salts (preferably the sodium, potassium orcalcium salts) of the these compounds.

An orally consumable material according to the present invention, inparticular a ready-to-drink composition according to the presentinvention, preferably comprises a total amount of less than 4.5 wt. %fats and fatty oils (i.e. triglycerides), more preferably less than 3.5wt. % fats and fatty oils, even more preferably less than 2.0 wt. % fatsand fatty oils, particularly preferably less than 1.0 wt. % fats andfatty oils, and most preferably less than 0.5 wt. % fats and fatty oils,in each case based on the total weight of the orally consumablematerial.

An orally consumable material according to the present invention, inparticular a ready-to-drink composition according to the presentinvention, preferably comprises a total amount of less than 5.0 wt. %proteins, more preferably less than 4.0 wt. % proteins, even morepreferably less than 3.0 wt. % proteins, particularly preferably lessthan 1.0 wt. % proteins, and most preferably less than 0.5 wt. %proteins, in each case based on the total weight of the orallyconsumable material.

Preferred orally consumable materials according to the present inventionare alcoholic or non-alcoholic beverages (preferably coffee-containingbeverages, tea-containing beverages, cocoa-containing beverages,wine-containing drinks, beer-containing drinks, fruit-containing softdrinks, isotonic drinks, soft drinks, energy drinks, nectars, fruit andvegetable juices, instant beverage powders after dilution in water,beverage concentrates, beverage syrups, fountain syrups, smoothies),dairy products (preferably flavoured milk, yoghurts, yoghurt drinks,kefir, buttermilk drinks, milk shakes, milk mix beverages), ice products(water ice, ice cream), fruit preparations (preferably sorbets, fruitsauces, fruit fillings, fruit ice creams), vegetable products(preferably soy milk products, ketchup, sauces), emulsions (preferablymayonnaise, remoulade, dressings, bakery flavour emulsions), jams,jellies, bakery fillings, pickle brine, frozen juice compositions, sourconfections, fruit pie fillings, desserts, marinades, and soups.

A (preferably acidic) beverage of this invention may be prepared, forexample, from a corresponding (preferably acidic) syrup compositionbased on a dilution or a throw of the (preferably acidic) syrup. Thoseskilled in the art recognize that a common throw for a soft drink, e.g.a cola-flavoured carbonated soft drink, is 1+5 so that a preparer usesone part of cola syrup and five parts water to prepare the (preferablyacidic) beverage from the (preferably acidic) syrup. The amount of(preferably acidic) syrup employed to prepare the (preferably acidic)beverage of this invention will of course vary depending on theconcentration of the syrup and the desired end product. Such amount canbe readily determined by those of ordinary skill in the art.

In a preferred embodiment, an orally consumable material according tothe present invention, in particular a ready-to-drink compositionaccording to the present invention, is clear. The term “clear” in thecontext of the present invention refers to a composition of matterhaving a turbidity of less than 25 FNU (Formazin Nephelometric Units) asmeasured according to DIN EN ISO 7027-Water quality-Determination ofturbidity (ISO 7027:1999).

Preferably, an orally consumable material according to the presentinvention, in particular a ready-to-drink composition according to thepresent invention, has a turbidity of less than 12 FNU, more preferablyof less than 6 FNU, preferably measured with a Hach Turbidimeter 2100NIS.

Preferred orally consumable materials according to the present inventionare in particular clear or turbid (carbonated or non-carbonated)beverages, preferably selected from the group consisting of lemonade,carbonated soft drinks, tea, ice-tea, beer-lemonade mixes, cola,beer-cola mixes, whey drink lemonade, tea, beer-lemonade mixtures, coladrinks, beer-cola mixes, and whey drinks, and the concentrates forproducing said beverages.

An orally consumable material according to the present invention (asdefined above) at 20° C. and 1013 mbar preferably is pourable, and morepreferably liquid.

An orally consumable material according to the present invention, inparticular a ready-to-drink composition according to the invention,preferably has dynamic viscosity value of smaller than 1250 mPa s (mPas=milli Pascal seconds; equal to cP=centiPoise), preferably of smallerthan 600 mPa s, more preferably of smaller than 250 mPa s, particularlypreferably of smaller than 100 mPa s, especially preferably of smallerthan 50 mPa s, and most preferably of smaller than 25 mPa s, in eachcase measured at 20° C. and at a shear rate of D=10 s⁻¹, e.g. asdetermined with a Brookfield® viscometer according to DIN 53018.

An orally consumable material according to the present invention, inparticular a ready-to-drink composition according to the invention,preferably has dynamic viscosity value in the range of from 1 to 1000mPa s (mPa s=milli Pascal seconds; equal to cP=centiPoise), preferablyin the range of 2 to 500 mPa s, more preferably in the range of 2 to 125mPa s, particularly preferably in the range of 3 to 50 mPa s, especiallypreferably in the range of 3 to 25 mPa s, in each case measured at 20°C. according to DIN 53018.

The flavour of an orally consumable material according to the presentinvention, in particular of a ready-to-drink composition according tothe present invention, preferably is selected from the group consistingof berries, citrus fruits, pomaceous fruit, spices, herbs, mints, teas,coffees, milk and/or milk products, and more particularly preferablyselected from the group consisting of cola, lemon, lime, lemon-lime,grapefruit, orange, sweet orange, bitter orange, bergamot, mandarin,apple, pear, prickly pear, peach, apricot, pineapple, prune, mango,melon, plum, kiwi, lychee, banana, cherry, sweet cherry, strawberry,raspberry, red currant, black currant, blackberry, blueberry, passionfruit, grape, pomegranate, acerola, vanilla, cinnamon, anise, fennel,clove, cardamom, tamarind, nutmeg, allspice, black pepper, honey,licorice, ginger ale, ginger, root beer, rose hip, green tea, red tea,rooibos tea, mate tea, honeybush tea, pu-erh tea, oolong tea, black tea,kombucha, milk, coffee, espresso, cocoa, chocolate, hazelnut, walnut,almond, peppermint, spearmint, wintergreen and mixtures thereof.

In a preferred embodiment, an orally consumable material according tothe present invention, in particular a ready-to-drink compositionaccording to the present invention, comprises one or more aminocarboxylic acids and/or one or more amino sulfonic acids, preferablygamma-amino butyric acid and/or taurine (2-aminoethanesulfonic acid).

An orally consumable material according to the present invention, inparticular a ready-to-drink composition according to the presentinvention, may preferably comprise one or more fruit derivedingredients, in particular fruity flavours, fruit juices, fruit pureesand fruit juice concentrates.

Fruit juices or fruit juice concentrates that can be used are preferablyderived from citrus fruits such as orange, lemon, grapefruit andtangerine, and other fruits such as apple, pear, grape, apricot andpineapple. Furthermore, fruit juices and fruit juice concentrates may bederived from soft fruits like blackberry, gooseberry, currant,blueberry, elderberry, strawberry and raspberry.

Preferably, an orally consumable material according to the presentinvention, in particular a ready-to-drink composition according to thepresent invention, is an emulsion. Densities of the disperse phase,which are preferred for an adequate stabilization and avoidance ofringing, preferably lie in the range of from 0.92 to 1.06 g/ml, morepreferably in the range of from 0.94 to 1.03 g/ml. “Ringing” is theformation of a ring around the neck of a (beverage) container which issought to be avoided.

If an orally consumable material according to the present invention, inparticular a ready-to-drink composition according to the presentinvention, comprises one or more weighting agents, these are preferablyselected from the group consisting of sucrose acetate isobutyrate (SAIB,E 444), estergum (E 445), dammar gum, and brominated vegetable oils inan amount not exceeding the respective legally authorizedconcentrations.

In a preferred embodiment, an orally consumable material according tothe present invention, in particular a ready-to-drink compositionaccording to the present invention, is a cloudy (turbid) emulsion,preferably comprising one or more clouding agents, such as titaniumdioxide, palm oil, or terpene oils like limonene.

If an orally consumable material according to the present invention, inparticular a ready-to-drink composition according to the presentinvention, is an emulsion, e.g. prepared as described in U.S. Pat. No.5,616,358, EP 2 025 250 or EP 1 151 677.

If an orally consumable material according to the present invention, inparticular a ready-to-drink composition according to the presentinvention, is a cloudy (turbid) emulsion, the D90 particle (droplet)size of the disperse phase (as measured by laser diffraction) is in therange of from 0.15 to 1.0 μm (microns), in some preferred embodiments inthe range of from 0.35 to 0.5 μm, in some other preferred embodiments inthe range of from 0.6 to 0.75 μm.

In a preferred embodiment, a beverage according to the present inventioncomprises a terpene oil, more preferably a terpene citrus oil. Preferredterpene oils in the context of the present invention comprise or consistof orange, lemon and/or grapefruit oils and fractions thereof,preferably limonene (especially D-limonene) and/or orange oil terpenes.

A material according to the present invention, preferably a food orcosmetic product according to the present invention, may additionallycomprise one or more physiological cooling agents, preferably selectedfrom the group consisting of menthone derivatives (preferably L-menthoneglycerol ketal), p-menthane-3,8-diol, cubebol, isopulegol and its esters(preferably L-(−)-isopulegol, L-(−)-isopulegol acetate), menthyl ethers(preferably (L-menthoxy)-1,2-propanediol,(L-menthoxy)-2-methyl-1,2-propanediol, L-menthyl-methyl ether), menthylesters (preferably menthyl formate, menthyl acetate, menthylisobutyrate, menthyl lactate, L-menthyl-L-lactate, L-menthyl-D-lactate,L-menthyl-(2-methoxy)acetate, L-menthyl-(2-methoxyethoxy)acetate,L-menthyl pyroglutamate), menthyl carbonates (preferably L-menthylpropylene glycol carbonate, L-menthyl ethylene glycol carbonate,L-menthyl glycerol carbonate or mixtures thereof), semi-esters ofmenthols with a dicarboxylic acid or derivatives thereof (preferablymenthyl oxamate, menthyl-N-methyloxamate, menthyl-N-ethyloxamate,mono-L-menthyl succinate, mono-L-menthyl glutarate, mono-L-menthylmalonate, O-L-menthyl succinic acid ester-N,N-(dimethyl)amide,O-L-menthyl succinic acid ester amide),2,3-dimethyl-2-(2-propyl)-butanoic acid derivatives (preferably2,3-dimethyl-2-(2-propyl)-butanoic acid-N-methyl amide [WS-23]),menthane carboxylic acid amides (preferably L-menthane carboxylicacid-N-ethyl amide [WS-3], N^(α)-(L-menthanecarbonyl)glycine ethyl ester[WS-5], menthane carboxylic acid-N-(4-methoxphenyl)-amide [WS-12],L-menthane carboxylic acid-N-tert-butyl amide [WS-14], L-menthanecarboxylic acid-N-(4-cyanophenyl)amide, N-(4-cyanomethylphenyl)p-menthanecarboxamide), L-menthane carboxylicacid-N-(alkoxyalkyl)amides, L-menthane carboxylicacid-N-(alkylthioalkyl)amides, and pyrrolidone derivatives ofcycloalkyldione derivatives (preferably3-methyl-2(1-pyrrolidinyl)-2-cyclopenten-1-one).

In one aspect of the present invention, preferred cosmetic products ofthe invention are oral hygiene products (oral care products). Preferredoral hygiene products are creams, gels, pastes, foams, emulsions,suspensions, aerosols, sprays or chewing gums. Such formulations serveto clean and care for the tooth substance and oral cavity and to freshenthe breath. More preferred oral hygiene products are toothpastes, toothgels, 2-in-1 tooth gels, mouthwashes, mouth rinses, gargles and mouth orbreath sprays.

A cosmetic, in particular an oral hygiene oral product according to theinvention can contain further auxiliary substances such as areconventionally used in such preparations, for example furtherpreservatives, abrasives, antibacterial agents, anti-inflammatoryagents, irritation-preventing agents, irritation-inhibiting agents,further antimicrobial agents, antioxidants, astringents, antisepticagents, antistatics, binders, buffers, support materials, chelatingagents, cell stimulants, cleansing agents, conditioning agents, furthersurface-active substances, deodorising agents, softeners, emulsifiers,enzymes, essential oils, film formers, foaming agents, foam stabilisers,substances to prevent foaming, gelling agents, moisturizing substances,moisture-retaining substances, bleaching agents, optical brighteners,dirt-repelling agents, lubricants, opacifiers, brighteners, polymers,powders, proteins, silicones, skin-calming agents, skin-cleansingagents, skin care agents, skin-healing agents, skin-cooling agents,skin-warming agents, stabilisers, thickeners, vitamins, oils, waxes,fats, phospholipids, saturated fatty acids, mono- or polyunsaturatedfatty acids, alpha-hydroxy acids, polyhydroxy fatty acids, dyes,colour-protecting agents, pigments, aroma substances, perfumes, andother conventional constituents, such as alcohols, polyols,electrolytes, organic solvents, sweeteners, sugar substitutes, silicas,calcium carbonate, calcium hydrogen phosphate, aluminium oxide,fluorides, zinc, tin, potassium, sodium and strontium salts,pyrophosphates, hydrogen peroxide, and hydroxyapatites.

Examples of aroma substances which can preferably be part of an oralhygiene product according to the invention are: anethole, menthol,menthone, isomenthone, menthyl acetate, menthyl propionate, menthofuran,mintlactone, eucalyptol (1,8-cineol), limonene, eugenol, eugenolacetate, isoeugenol methyl ether, thymol, pinene, sabinene hydrate,3-octanol, carvone, gamma-octalactone, gamma-nonalactone, germacrene-D,viridiflorol, 1,3E,5Z-undecatriene, isopulegol, piperitone, 2-butanone,ethyl formate, 3-octyl acetate, isoamyl isovalerianate, hexanol,hexanal, cis-3-hexenol, linalool, alpha-terpineol, cis- and trans-carvylacetate, p-cymol, damascenone, damascone, rose oxide, fenchol,acetaldehyde diethylacetal, 1-ethoxyethyl acetate, cis-4-heptenal,isobutyraldehyde, isovaleraldehyde, cis-jasmone, methyldihydrojasmonate, anisaldehyde, methyl salicylate,2′-hydroxpropiophenone, menthyl methyl ether, myrtenyl acetate,2-phenylethyl alcohol, 2-phenylethyl isobutyrate, 2-phenylethylisovalerate, cinnamaldehyde, geraniol, nerol. In the case of chiralcompounds the aroma substances can be used as a single enantiomer or amixture of enantiomers, e.g. in the form of a racemate.

Aroma substances which preferably are part of an oral hygiene productaccording to the invention are preferably selected from the groupconsisting of aniseed oil, basil oil, bitter almond oil, camphor oil,citronella oil, citrus oils, eucalyptus citriodora oil, eucalyptus oil,camomile oil, spearmint oil, limette oil, mandarin oil, clove oil,orange oil, peppermint oil, sage oil, thyme oil, wintergreen oil,cinnamon oil, cinnamon bark oil, l-menthol, menthone, isomenthone,1,8-cineol (eucalyptol), carvone, alpha-terpineol, methyl salicylate,2′-hydroxpropiophenone, and menthyl methyl ether.

Another group of preferred cosmetic products of the invention aresanitary articles, preferably selected from the group consisting of wetwipes, sanitary towels, diapers, tampons, handkerchiefs and refreshingtissues containing one or more compounds of formula I (to be used)according to the invention and/or one or more physiologically acceptablesalts thereof. Said sanitary articles according to the inventionpreferably contain a material according to the present invention, inparticular in one of the preferred variants described herein.

In a non-woven system, preferably at least one layer comprises anabsorbent non-woven fabric or a porous polymer which is impregnated witha solution or suspension comprising one or more compounds of formula I(to be used) according to the invention and/or one or morephysiologically acceptable salts thereof, and preferably comprises oneor more additional other active substances (such as skin-soothing and/orskin-moisturizing agents).

The following Examples illustrate the invention without limiting itsscope.

EXAMPLES

Abbreviation Definition ppm = μg/mL Part per million identical withmicro gram per millilitre ACN Acetonitrile CFU Colony forming units ELSDEvaporative Light Scattering Detection HPGPC High Performance GelPermeation Chromatography HPLC High Performance Liquid ChromatographyHR-ESIMS High Resolution Electrospray Ionisation Mass Spectrometry LCTLiquid Chromatography Time of Flight MS Mass Spectrometry TFATrifluoroacetic acid UV/Vis Ultraviolet/visible light

Example 1 Cultivation A) Media:

-   1) SDB (Sabouraud Dextrose Broth, Ref. 238230, Difco™ Lawrence,    Kans., USA, containing 0.5% Peptic Digest of Animal Tissue, 0.5%    Pancreatic Digest of Casein, 2.0% Dextrose, pH 5.6.-   2) YMG (Yeast-Malt-Glucose) medium: D-glucose 0.4% (Merck,    Darmstadt, Germany, Ref. K25252846 831), malt extract 1% (Carl Roth,    Karlsruhe, Germany, Ref. X976.2), yeast extract 0.4% (Merck,    Darmstadt, Germany, Ref. 1.11926.1000), pH 6.3.-   3) PDB (Potato Dextrose Broth): 2.0% D-glucose, 0.4% mashed potatoes    (Pfanni, Hamburg, Germany).-   4) Cornmeal medium (CM): 2.0% corn meal (Neuform, Zarrentin,    Germany), 1.0% D-glucose.-   5) GM1 (Glucose-Yeast medium 1): 2.0% D-glucose, 0.5% yeast extract.-   6) GM2 (Glucose-Yeast medium 2): 2.0% D-glucose, 0.1% yeast extract.-   7) Malt medium 1: 2.0% malt extract, 0.5% yeast extract.-   8) Malt medium 2: 2.0% malt extract without yeast extract.-   9) Apple juice medium: 10% apple juice (common commercial product:    clear juice, EAN 20009717, Fruchtstern®, trademark by Netto    Marken-Discount AG & Co. KG, Maxhütte-Haidhof, Germany), 4.83%    glucose, 5.94% fructose, 0.23% sucrose, 0.1% (v/v) hardness solution    (prepared from 4.4 g CaCl₂*2H₂O+3.04 g MgCl₂*6H₂O dissolved in 100    ml water), 0.2% (v/v) 1M sodium malate, 0.2% (v/v) 1M maleic acid;    adjusted to pH 3.2-3.4 with 1M maleic acid.-   10) Trypticase Soy Yeast Extract medium: 3% Trypticase soy broth    (Difco, Lawrence USA, Ref. 211825), 0.3% Yeast extract (Merck,    Darmstadt Germany, Ref. 111926).

B) Fermentation (Exemplarily Presented Using the Strain FU50088) a) SeedCultures (Shake Flask Cultures)

One ml of a cryo vial containing a mycelial suspension of FU50088 in 10%glycerol was retrieved from liquid nitrogen and, after thawing, used toinoculate 200 ml Erlenmeyer flasks containing 50 ml of sterile YMGmedium and propagated on a rotary shaker at 240 rpm and 23° C. for 72 h.Thereafter, each two ml of the primary seed culture were transferredinto batches of two 500 ml Erlenmeyer flasks containing 200 ml of thesame medium and propagated on a rotary shaker at 140 rpm and 23° C. for120 h. These flasks served as secondary seed cultures.

b) Fermentation in 30 l Scale

A 40 l Biostat LP42 fermentor (Bioengeneering, Wald, Switzerland)containing 301 of medium was sterilized in situ (1 h at 121° C. and 1.1bar) and inoculated with 400 ml of the secondary seed culture. Theproduction culture was grown under stirring (240 rpm) and aeration (0.2vvm (volumes of air per minute per volume of batch)) at 30° C.

Furthermore at each point of incubation time listed above, HPLC analysisof crude extracts prepared from 20 ml samples taken under sterileconditions and extracted with equal amounts of ethyl acetate served as ameans of detection and estimation of glycolipids. For this purpose, theethyl acetate extracts are dried over anhydrous sodium sulfate,evaporated to dryness, re-dissolved in 2-propanol and analyzed using theHPLC systems described below in HPLC-MS methods “fermentation control”.

TABLE A Dependency of yield on nutrient composition ProductionExtractable Diameter of inhibition Culture maximum [h Mycelial drymaterial zone (mm)** medium fermentation] pH value weigth [g/l] [g/l] B.subtilis S. cerevisiae SDB 192 4.6 6.2 0.26 18 10 YMG 216 6.0 4.8 0.1312 0 PDB 312 4.7 1.7 0.76 18 9 CM 216 4.6 * 0.65 17 14 GM1 312 4.7 4.30.69 20 13 GM2 192 4.1 3.3 1.26 20 13 MM1 192 5.2 12.8 0.24 18 11 MM2192 4.4 8.0 1.07 19 15 *Mycelial weight was not determined (mediumcontaning solid constitutents) **Inhibition zones caused after 24 h by50 μg of ethyl acetate extract dissolved in methanol on a paper disk (6mm diameter)

For optimisation of culture media, Dacryopinax spathularia waspropagated in a series of 500 ml shake flask batches containing each 200ml of culture media as described above (Example 1B) under “a) Shakeflask cultures (including “Seed cultures). During fermentation, sampleswere taken, and pH, mycelial dry weight, amount of extractable materialand biological activities of crude ethyl acetate extracts of the culturebroth against Bacillus subtilis and Zygosaccharomyces bailii in the agardiffusion assay were determined. The results (Table A) show that, eventhough the glycolipids are produced in a variety of different culturemedia, GM2 medium showed the highest specific biological activity withrespect to the mycelial dry weight and the fermentation time. As itcould even be observed during fermentation by microscopic control thatthe glycolipids sticked to the mycelial hyphae during the productionphase, it was deemed favorable to use GM2 medium for large scalefermentation, in order to direct the majority of the products to belocated in the culture broth, especially in view of the precipitationexperiments that were finally found the most effective and ecologicallyfriendly way of obtaining the desired compounds. In addition, themaximum of production was obtained earlier than in most otherfermentation media.

c) Fermentation in 200 l Scale

The fermentation was performed in a 3001 fermentor (Bioengineering TypeP, equipped with four Ekato Intermig® impellers) containing 200 l of GM2medium, sterilized under steam for 45 min at 121° C., inoculated withthe above described 20 l seed culture. To prevent foaming, 0.03 ml/l ofClarol FBA 3003K (Cognis, Monheim, Germany) as anti-foam agent wereadded; no additional supply of antifoam was necessary duringfermentation. The fermentation was performed at ca. 33° C., underagitation (75 rpm) and aeration (0.2 vvm). The fermentation was stoppedafter 300 h when the free glucose had almost been consumed and theoxygen partial pressure had dropped to 20%.

C) Preparation of Extracts a) Preparation of Mycelial Extract:

The cultures from 10 shake flasks were harvested. The culture fluid wasseparated by filtration from the mycelia. The wet mycelia were extractedtwo times with equal volumes of acetone for each 30 min in an ultrasonicbath. This acetone was evaporated in vacuo at 40° C. and the remainingaqueous phase was diluted to 700 ml with water. This phase was extractedthree times with equal volumes of ethyl acetate (EtOAc). The combinedorganic phases were dried over anhydrous Na₂SO₄ and evaporated in vacuoto yield 329 mg of a crude extract.

b) Preparation of the Culture Fluid Extract:

1000 g Amberlite® XAD16 (Sigma-Aldrich, St. Louis, Mo. 63103, CAS90003-69-4, Batch-No. 099K0079) were added to 301 culture filtrate (froma 30 l fermenter, GM2 medium) and incubated over night under stirring(60 rpm). The resin was harvested by filtration and the dry resin wasincubated with two liters of methanol and incubated for 30 min in anultrasonic bath. Thereafter, the methanol eluate was removed byfiltration. This methanol elution process was repeated twice. Themethanol eluates (ca. 6 l) were combined evaporated in vacuo and theresulting oily residue redissolved in 500 ml distilled water. The pH wasadjusted with 2 M HCl to pH 2.9, and the resulting suspension wasextracted three times each with equal amounts of ethyl acetate. Thecombined organic phases were dried over sodium sulfate, evaporated invacuo (40° C.) to yield 25 g of an amorphous, light brown crude extract.

c) Preparation of a Sedimentation (Precipitation) (DownstreamProcessing) Product

The culture broth resulting from a 2001 fermentation was alkalized froman initial pH value of 4.5 to pH 8 with 1 N sodium hydroxide solution toallow the glycolipids that partially stick to the cells under acidicconditions to become largely released from the mycelia. After 1 h themycelia were separated using a Westfalia KA1-06-525 separator, and inaddition the culture broth was filtrated through a Pall (DreieichGermany) 0.1 μm polysulfone membrane filter casettes, diameter of fibers1.4 mm, total area 24 m²) microfiltration system to completely retainthe mycelia. The product was sedimented (precipitated) by acidifying thefiltrate with 2 N hydrochloric acid to pH 3 and incubating for 16 hunder cooling to 11° C. The fluid was removed by decantation andsubsequent centrifugation (4500 rpm, 15 min, Typ Jouan SA LR 5.22(Jouan, Paris France), resulting in a whitish-grey gel. This crudeproduct was washed immediately with water (pH 7), centrifuged again at(4500 rpm for 15 min) and freeze-dried. This process yielded 380 g dryglycolipid which was further characterized by HPLC-MS (see e.g. HPLCchromatogram in FIG. 2).

D) Isolation of Compounds a) Flash Chromatography

10 g of the raw product were dissolved in 5 ml of methanol and boundonto 10 g of Chromabond XTR (Kieselguhr for liquid-liquid extractionMacherey-Nagel, Article No. 730 595.500, Düren, Germany) and the solventwas evaporated in vacuo. This dried material was applied onto a BiotageIsolera (Uppsala, Sweden) MPLC system, using a Chromabond® flash (120Nucleodur 100-20 C18ec; 130×40 mm) (trademark by Macherey-Nagel) asstationary phase.

The column was equilibrated with ACN/water (1:5) and then eluted usingthe following conditions at a flow of 20 ml/min: 3:30 min, ACN/water(1:5) isocratic; 9 min, ACN/water (1:1) gradient; 19:00 min, ACN/water(1:1) isocratic; 29:00 min ACN/water (2:1) gradient; 49:00 min ACN/water(2:1) isocratic; 59:00 min pure ACN gradient.

Small aliquots of the fractions were taken, evaporated and dissolved in2-propanol to concentrations of 5 mg/ml and analyzed by HPLC-MS usingthe “Adapted Method” as described in Example 3. The fractions werecombined according to HPLC-MS results and concentrated in vacuo.

Fractions containing the compounds of the formula I elute according thefollowing table.

TABLE 2 Flash chromatographic elution profile of compounds of theformula I Elution time Containing compound Yield [min] number [mg] 17-26[16] 686 27-29 [14] 791 32-33 [12] 505 34-35 [13] 542 36-38  [1] 125641-48 [18] 570

b) Purification by HPLC

All these separation steps were performed with

-   CA: Waters SunFire C18 preparative HPLC column (7 μm, length 250    mm*diameter 19 mm)-   CB: Kromasil C18 (7 μm, length 250 mm*diameter 40 mm)+pre column    (Kromasil C18, 7 μm, length 50 mm*diameter 20 mm)-   CC: Kromasil C8 (7 μm, length 250 mm*diameter 40 mm)-   CD: lnertsil ODS-3 C18 (5 μm, length 250 mm*diameter 40 mm)    as stationary phase. The eluent was built up with ACN and water    using a flow rate of 10 ml/min. The maximal capacity of this column    is about 600 mg. Therefore it was necessary to perform several    identical purifications in series in order to purify larger amounts.

The separations were monitored by a diode array detector at 200 and 210nm. Five ml fractions were taken using an automatic fraction collectorand finally combined according to UV absorption (200 and 210 nm),concentrated in vacuo and subjected to HPLC-MS, to assess their purity.

For those skilled in the art it is obvious to adapt the elutionmethodology to the retention necessities of each compound, e.g. lesspolar compounds will elute later, consequently it is possible to startwith a higher content of ACN in the eluent. Sometimes it is better touse another slope of the gradient or it is necessary to use an isocraticsystem.

TABLE 3 HPLC purification elution profiles of compounds of the formula IPurified Retention Column Gradient compound time [min] code flow Purity(NMR) [16] I CB 10 min: ACN 50% 85% (NMR) 6.5-8.5 30 min: ACN 50% → 80%45 min: ACN 80% 50 min: ACN 80% → 85% 70 min: ACN 85% 90 min: ACN 85% →100% 20 ml/min [14] I CC 15 min: MeOH 20% → 50%, 49.5-54   70 min: MeOH50% → 100%, 100 min: MeOH 100%, 20 ml/min II CD 15 min: ACN 20% → 45%,75% (NMR) 26.5-28.5 30 min: ACN 45% 35 min: ACN 45% → 50%, 50 min: ACN50% 55 min: ACN 50% → 55%, 70 min: ACN 55% 90 min: ACN 55% → 100%, 100min: ACN 100% 20 ml/min [12] I CB 10 min: ACN 50% 95% (NMR) 19.5-21   30min: ACN 50% → 80% 45 min: ACN 80% 50 min: ACN 80% → 85% 70 min: ACN 85%90 min: ACN 85% → 100% 20 ml/min [13] I CC 15 min: MeOH 20% → 50%, 55-5670 min: MeOH 50% → 100%, 100 min: MeOH 100%, 20 ml/min II CD 15 min: ACN 20% → 50%, 85% (NMR) 35-36 30 min: ACN 50% 35 min: ACN 50% → 55%, 50min: ACN 55% 55 min: ACN 55% → 60%, 70 min: ACN 60% 90 min: ACN 60% →100%, 100 min: ACN 100% 20 ml/min  [1] I CB 10 min: ACN 50% 95% (NMR)35-36 min.     30 min: ACN 50% → 80% 45 min: ACN 80% 50 min: ACN 80% →85% 70 min: ACN 85% 90 min: ACN 85% → 100% 20 ml/min [18] I CA 15 min:ACN 20% → 50%, 42 min 35 min: ACN 50%, 40 min: ACN 50% → 100%, 50 min:ACN 100%, 20 ml/min II CA 40 min: ACN 40% → 100%, 93% (NMR) 17 min 45min: ACN 100%, 20 ml/min

Exemplarily the purification of compound [1] is described herein indetail: The elution profile was running from: 10 min isocratic ACN 50%;30 min gradient ACN 50%→80%; 45 min isocratic ACN 80%; 50 min gradientACN 80%→85%; 70 min isocratic ACN 85%; 90 min gradient ACN 85%→100% witha flow of 20 ml/min using column CB (Kromasil C18). Within a retentiontime of 35-36 min compound [1] eluted from the above described system.The purity was determined as 95% by ¹H-NMR.

E) Definition of Extracts

Extracts containing compounds of the formula I are defined with theirpreparation procedures, e.g. the use of the above explained processes.

TABLE 4 Preparation Extract Fermentation of extracts id Strain process Bprocess C Full process code [X1] MUCL53181 example 1, B b) example 1, Cc) MUCL53181 example 1, B b), C c) [X2] MUCL53181 example 1, B c)example 1, C c) MUCL53181 example 1, B c), C c) [X3] MUCL53181 example1, B a) example 1, C a) MUCL53181 example 1, B a), C a) [X4] MUCL53182example 1, B a), example 1, C b) MUCL53182 example 1, B a), C b) [X5]MUCL53179 example 1, B a), example 1, C a) MUCL53179 example 1, B a), Ca) [X6] MUCL53500 example 1, B b), example 1, C c) MUCL53500 example 1,B b), C c)

Exemplarily the codation of [X1] is described herein in detail: The useof the strain FU50088 of the species Dacryopinax spathularia in afermentation procedure as described above in the example 1 “Cultivation”with a process as described in this example under section B“fermentation” using a 30 l fermentor as described in this section undersubsection b) “30 l fermentations” followed by a preparation procedureas described in the same example 1 with a process as described undersection C “Preparation of extracts” using a precipitation process asdescribed in this section under subsection c) “Preparation of asedimentation product” is coded as “an extract of FU50088 accordingexample 1 using a production process B b) and an extraction process Cc)” or in short terms “extract FU50088 example 1, B b), C c)”.

Example 2 Structural Characterisation Compound No. [1]

The molecular structure was elucidated by thorough interpretation ofhigh resolution mass spectrometric data and 1D and 2D NMR spectra. Thestructural characterisation follows the general methodology which isknown to the person skilled in the art and described in more detail inthe scientific literature (examples: Nishida et al., J. Antibiot. 1991,44, 541; Nishida et al, Chem. Pharm. Bull. 1991, 39, 3044).

The numbering of the atoms is shown in FIG. 1.

Chemical Formula: C₄₉H₈₈O₂₁

Exact Mass: 1012.5818 Da

Molecular Weight: 1013.2104 Da

HR-ESIMS: found m/z 1013.5874; calculated m/z 1013.5891 for [M+H]⁺

NMR spectra were obtained in CD₃OD at 293 K on a Bruker DRX spectrometeroperating at 500 MHz proton frequency. The residual solvent peak wasused as internal reference (δ_(H)=3.30; δ_(C)=49.0). The assigned NMRdata are summarized in Tables 5-14.

TABLE 5 NMR data for Compound No. [1] aglycon moiety carbohydrate moietyatom δ_(C) δ_(H), mult. atom δ_(C) δ_(H), mult. 1 178.1 — 1′   102.54.38, d (4.7) 2 71.4 4.09, dd (7.6, 4.4) 2′   84.5 3.25, m 3 35.4 1.63,1.74, m 3′   77.1 3.52, m 4 26.2 1.42, m 4′   70.6 3.50, m 5 30.7 1.33,m 5′   66.6 3.16, 3.83, m 6-14 30.8 1.30, m 1″  104.2 4.61, d (7.1) 1526.9 1.33, 1.53, m 2″  83.1 3.51, m 16 33.5 1.33, 1.60, m 3″  74.4 3.80,m 17 76.0 3.36, m 4″  72.9 4.69, m 18 76.0 3.36, m 5″  63.5 3.23, 3.96,m 19 33.5 1.33, 1.60, m 1″′ 105.4 4.67, d (7.6) 20 22.6 1.36, 1.62, m2″′ 75.6 3.25, m 21 35.9 1.54, m 3″′ 11.1 3.37, m 22 80.1 3.62, m 4″′71.4 3.30, m 23 35.4 1.43, 1.45, m 5″′ 76.0 3.53, m 24 28.5 1.33, 1.38,m 6″′ 64.4 4.21, 4.49, m 25 24.2 0.92, 1.32, m 4″—O—COCH₃ 172.5 — 2614.6 0.92, t (6.8) 4″—O—COCH ₃ 20.8 2.06, s 6″′—O—COCH₂CH(CH₃)₂ 174.8 —6″′—O—COCH ₂CH(CH₃)₂ 44.2 2.29, d (7.1) 6″′—O—COCH₂ CH(CH₃)₂ 26.9 2.10,m 6″′—O—COCH₂CH(CH ₃)₂ 23.0 0.98, d (6.8)

TABLE 6 NMR data for Compound No. [13] aglycon moiety carbohydratemoiety atom δ_(C) δ_(H), mult. atom δ_(C) δ_(H), mult. 1 178.3 — 1′  102.3 4.40, d (6.8) 2 71.5 4.08, m 2′   84.0 3.27, m 3 35.4 1.62, 1.74,m 3′   77.2 3.51, m 4 26.1 1.42, m 4′   70.7 3.50, m 5 30.6 1.33, m 5′  66.5 3.17, 3.86, m 6-14 30.2 1.29, m 1″  104.1 4.60, d (6.8) 15 26.91.33/1.52, m 2″  83.4 3.44, t (7.9) 16 33.4 1.32/1.60, m 3″  77.2 3.55,m 17 76.0 3.36, m 4″  70.7 3.50, m 18 76.0 3.36, m 5″  66.5 3.17, 3.86,m 19 33.4 1.32/1.60, m 1″′ 105.4 4.71, d (7.6) 20 22.4 1.36/1.62, m 2″′75.8 3.36, m 21 35.8 1.55, m 3″′ 75.5 3.57, m 22 80.1 3.62, m 4″′ 72.04.83, m 23 35.2 1.45, m 5″′ 73.6 3.72, m 24 28.3 1.33, m 6″′ 63.4 4.19,m 25 24.0 1.31, m 4″′—O—COCH₃ 171.8 — 26 14.5 0.91, t (6.5) 4″′—O—COCH ₃20.9 2.06, s 6″′—O—COCH₂CH(CH₃)₂ 174.9 — 6″′—O—COCH ₂CH(CH₃)₂ 44.0 2.26,d (7.1) 6″′—O—COCH₂ CH(CH₃)₂ 26.7 2.08, m 6″′—O—COCH₂CH(CH ₃)₂ 22.90.96, d (7.0)

TABLE 7 NMR data for Compound No. [16] aglycon moiety carbohydratemoiety atom δ_(C) δ_(H), mult. atom δ_(C) δ_(H), mult. 1 178.3 — 1′  102.3 4.43, d (6.5) 2 71.0 4.09, dd (7.1, 4.1) 2′   83.6 3.31, m 3 35.81.62, 1.74, m 3′   76.3 3.57, m 4 26.1 1.42, m 4′   70.7 3.51, m 5 30.51.33, m 5′   66.1 3.18, 3.86, m 6-14 30.2 1.29, m 1″  104.2 4.61, m 1527.0 1.33/1.52, m 2″  84.0 3.44, m 16 33.4 1.32/1.60, m 3″  77.3 3.53, m17 75.7 3.36, m 4″  70.8 3.51, m 18 75.7 3.36, m 5″  66.8 3.18, 3.86, m19 33.5 1.32/1.60, m 1″′ 105.7 4.62, d (7.2) 20 22.6 1.36/1.62, m 2″′75.9 3.25, m 21 35.8 1.55, m 3″′ 77.3 3.35, m 22 80.1 3.62, m 4″′ 71.13.31, m 23 35.4 1.45, m 5″′ 78.8 3.31, m 24 28.4 1.33, m 6″′ 62.4 3.71,3.90, m 25 24.1 1.31, m 26 14.5 0.91, t (6.5)

TABLE 8 NMR data for Compound No. [17] aglycon moiety carbohydratemoiety atom δ_(C) δ_(H), mult. atom δ_(C) δ_(H), mult. 1 176.4 — 1′  102.3 4.44, d (6.8) 2 71.7 4.13, dd (7.6,4.6) 2′   83.6 3.31, m 3 35.31.64, 1.74, m 3′   76.4 3.57, m 4 25.8 1.42, m 4′   70.6 3.51, m 5 30.61.33, m 5′   66.2 3.19, 3.86, m 6-14 30.2 1.29, m 1″  104.2 4.61, d(6.5) 15 26.9 1.33/1.52, m 2″  84.0 3.43, t (7.8) 16 33.4 1.33/1.60, m3″  77.3 3.53, m 17 76.0 3.35, m 4″  70.9 3.51, m 18 76.0 3.35, m 5″ 66.7 3.17, 3.86, m 19 33.4 1.33, m 1″′ 105.9 4.62, d (7.4) 20 22.4 1.35,m 2″′ 75.9 3.25, m 21 35.8 1.53, m 3″′ 77.7 3.36, m 22 80.2 3.63, m 4″′70.9 3.31, m 23 33.4 1.46, m 5″′ 78.8 3.31, m 24 28.5 1.34, m 6″′ 62.53.71, 3.89, m 25 23.8 1.33, m 26 14.5 0.91, t (7.0) OMe 52.4 3.71, s

TABLE 9 NMR data for Compound No. [12] aglycon moiety carbohydratemoiety atom δ_(C) δ_(H), mult. atom δ_(C) δ_(H), mult. 1 178.0 — 1′  102.5 4.39, d (6.8) 2 71.5 4.09, dd (7.4, 4.4) 2′   84.4 3.26, m 3 35.51.62, 1.73, m 3′   77.4 3.52, m 4 26.1 1.42, m 4′   71.0 3.51, m 5 30.61.32, m 5′   66.5 3.18, 3.86, m 6-14 30.8 1.30, m 1″  104.3 4.55, d(6.8) 15 26.8 1.33, 1.52, m 2″  83.4 3.43, m 16 33.6 1.34, m 3″  76.93.55, m 17 76.0 3.36, m 4″  71.0 3.51, m 18 76.0 3.36, m 5″  66.5 3.18,3.86, m 19 33.5 1.34, 1.49, m 1″′ 105.4 4.65, d (6.8) 20 22.6 1.36,1.61, m 2″′ 75.7 3.28, m 21 35.8 1.53, m 3″′ 77.7 3.38, m 22 80.1 3.61,m 4″′ 71.5 3.30, m 23 35.4 1.47, 1.56, m 5″′ 75.7 3.52, m 24 28.4 1.33,m 6″′ 64.4 4.21, 4.49, m 25 24.1 1.32, m 6″′—O—COCH₂CH(CH₃)₂ 174.9 — 2614.5 0.91, t (6.8) 6″′—O—COCH ₂CH(CH₃)₂ 44.2 2.28, d (7.1) 6″′—O—COCH₂CH(CH₃)₂ 26.8 2.10, m 6″′—O—COCH₂CH(CH ₃)₂ 22.9 0.97, d (6.6)

TABLE 10 NMR data for Compound No. [14] aglycon moiety carbohydratemoiety atom δ_(C) δ_(H), mult. atom δ_(C) δ_(H), mult. 1 178.0 — 1′  102.3 4.42, d (6.3) 2 71.5 4.09, dd (7.4, 4.6) 2′   83.2 3.30, m 3 35.81.62, 1.74, m 3′   76.8 3.57, m 4 26.1 1.42, m 4′   70.7 3.50, m 5 30.51.33, m 5′   66.3 3.17, 3.85, m 6-14 30.2 1.29, m 1″  104.1 4.69, d(7.1) 15 26.9 1.34, 1.55, m 2″  83.5 3.44, t (7.9) 16 33.4 1.33, m 3″ 74.2 3.55, m 17 76.0 3.36, m 4″  72.9 3.50, m 18 76.0 3.36, m 5″  63.43.17, 3.86, m 19 33.4 1.33, 1.63, m 1″′ 105.8 4.71, d (7.6) 20 22.51.38, 1.63, m 2″′ 75.66 3.36, m 21 35.8 1.53, m 3″′ 77.2 3.57, m 22 80.23.63, m 4″′ 71.1 4.83, m 23 35.2 1.40, m 5″′ 78.7 3.72, m 24 28.4 1.32,m 6″′ 62.5 4.19, m 25 23.8 1.32, m 4″′—O—COCH₃ 172.2 — 26 14.5 0.91, t(6.5) 4″′—O—COCH ₃ 20.8 2.06, s

TABLE 11 NMR data for Compound No. [10] aglycon moiety carbohydratemoiety atom δ_(C)*⁾ δ_(H), mult. atom δ_(C)*⁾ δ_(H), mult. 1 179.1 —1′   102.0 4.39, d (6.8) 2 72.2 3.97, dd (7.4, 4.4) 2′   84.0 3.25, m 335.4 1.60, 1.73, m 3′   76.9 3.50, m 4 26.1 1.42, m 4′   70.4 3.49, m5-13 30.3 1.28, m 5′   66.3 3.17, 3.84, m 14 26.3 1.31, 1.42, m 1″ 103.9 4.63, d (6.8) 15 38.2 1.35, 1.42, m 2″  83.2 3.52, m 16 72.1 3.50,m 3″  74.1 3.79, m 17 38.2 1.35, 1.42, m 4″  72.6 4.68, m 18 22.0 1.35,1.51, m 5″  63.2 3.23, 3.97, m 19 35.7 1.51, m 1″′ 105.2 4.66, d (6.8)20 79.8 3.61, m 2″′ 75.4 3.27, m 21 34.6 1.44, 1.54, m 3″′ 77.4 3.36, m22 30.3 1.28, m 4″′ 71.0 3.33, m 23 30.3 1.28, m 5″′ 75.6 3.52, m 2432.8 1.28, m 6″′ 64.1 4.22, dd (11.7, 5.2), 4.46, d (11.7 25 23.4 1.33,m 4″—O—COCH₃ 171.8 — 26 13.9 0.91, t (6.8) 4″—O—COCH ₃ 20.5 2.06, s6″′—O—COCH₃ 172.6 — 6″′—O—COCH ₃ 20.7 2.10, s *⁾carbon chemical shiftsobtained from HSQC/HMBC experiments.

TABLE 12 NMR data for Compound No. [18] aglycon moiety carbohydratemoiety atom δ_(C)*⁾ δ_(H), mult. atom δ_(C)*⁾ δ_(H), mult. 1 178.1 —1′   102.5 4.38, d (6.8) 2 71.5 4.07, m 2′   84.4 3.25, m 3 35.5 1.63,1.74, m 3′   77.1 3.52, m 4 26.1 1.43, m 4′   70.6 3.51, m 5-13 30.61.30, m 5′   66.5 3.11, 3.84, m 14 26.0 1.35, 1.42, m 1″  104.3 4.62, d(6.5) 15 38.4 1.34, m 2″  83.3 3.52, m 16 72.4 3.50, m 3″  74.4 3.80, m17 38.4 1.34, m 4″  72.9 4.69, m 18 22.3 1.35, 1.51, m 5″  63.5 3.23,3.97, m 19 35.8 1.51, m 1″′ 105.4 4.66, d (7.6) 20 80.2 3.61, m 2″′ 75.63.26, m 21 34.9 1.44, 1.54, m 3″′ 111 3.36, m 22 30.6 1.30, m 4″′ 71.53.31, m 23 30.6 1.30, m 5″′ 75.9 3.53, m 24 33.4 1.27, m 6″′ 64.4 4.21,dd (11.7, 5.5), 4.56, d (11.7) 25 23.8 1.32, m 4″—O—COCH₃ 172.2 — 2614.5 0.91, t (6.8) 4″—O—COCH ₃ 20.8 2.06, s 6″′—O—COCH₃ 174.8 —6″′—O—COCH ₂CH(CH₃)₂ 44.2 2.29, d (7.1) 6″′—O—COCH₂ CH(CH₃)₂ 26.8 2.10,m 6″′—O—COCH₂CH(CH ₃)₂ 22.9 0.98, d (6.5)

TABLE 13 NMR data for Compound No. [7] aglycon moiety carbohydratemoiety atom δ_(C) δ_(H), mult. atom δ_(C) δ_(H), mult. 1 178.1 — 1′  102.5 4.47, d (6.8) 2 71.5 4.09, m 2′   85.3 3.33, m 3 35.4 1.64, 1.75,m 3′   74.2 3.77, t (9.1) 4 26.1 1.43, m 4′   73.0 4.71, m 5 30.7 1.33,m 5′   63.5 3.25, 3.95, m 6-14 30.7 1.30, m 1″  104.8 4.64, d (7.4) 1526.9 1.33, 1.53, m 2″  84.7 3.40, m 16 33.4 1.34, 1.59, m 3″  77.6 3.53,m 17 76.0 3.37, m 4″  70.9 3.51, m 18 76.0 3.37, m 5″  66.9 3.17, 3.84,m 19 33.4 1.34, 1.59, m 1″′ 106.1 4.64, d (7.6) 20 22.6 1.36, 1.61, m2″′ 76.0 3.27, m 21 35.8 1.54, m 3″′ 77.6 3.37, m 22 80.1 3.63, m 4″′71.1 3.33, m 23 34.8 1.47, m 5″′ 75.9 3.55, m 24 28.4 1.34, m 6″′ 64.64.18, dd (12.0, 5.7), 4.41, d (11.4) 25 23.8 1.33, m 4′—O—COCH₃ 172.2 —26 14.5 0.92, t (6.8) 4′—O—COCH ₃ 20.9 2.04, s 6″′—O—COCH₃ 172.7 —6″′—O—COCH ₃ 21.0 2.09, s

TABLE 14 NMR data for Compound No. [6] aglycon moiety carbohydratemoiety atom δ_(C) δ_(H), mult. atom δ_(C) δ_(H), mult. 1 178.2 — 1′  102.4 4.41, d (6.8) 2 70.7 4.12, m 2′   84.2 3.30, m 3 34.2 1.67, 1.78,m 3′   77.1 3.55, t (9.1) 4 24.6 1.46, m 4′   70.9 3.51, m 5 30.8 1.33,m 5′   66.4 3.21, 3.87, m 6-14 30.8 1.30, m 1″  104.2 4.62, d (7.1) 1527.0 1.33, 1.53, m 2″  83.6 3.40, m 16 34.5 1.34, 1.59, m 3″  77.3 3.53,m 17 75.7 3.37, m 4″  70.6 3.51, m 18 75.7 3.37, m 5″  66.7 3.17, 3.84,m 19 34.0 1.59, m 1″′ 105.5 4.73, d (7.6) 20 22.5 1.48, 1.55, m 2″′ 75.73.37, m 21 35.7 1.56, m 3″′ 75.2 3.59, m 22 80.2 3.63, m 4″′ 71.9 4.87,m 23 34.5 1.52, m 5″′ 73.5 3.73, m 24 28.4 1.36, m 6″′ 64.6 4.15, dd(11.0, 5.6), 4.22, d (11.7) 25 24.1 1.35, m 4″′—O—COCH₃ 172.2 — 26 14.50.93, t (6.8) 4″′—O—COCH ₃ 20.9 2.09, s 6″′—O—COCH₃ 172.7 — 6″′—O—COCH ₃20.9 2.09, s

Example 3 HPLC-UV-MS-ELSD Analysis A General Methods a) “StandardMethod”

LC-MS/UVELSD analyses were performed using an Agilent HP1100 (Agilent,Waldbronn, Germany) liquid chromatograph coupled with a LCT massspectrometer (Waters Corporation, Milford, Mass., USA) in the positiveand negative electrospray ionization (ESI) mode and a Sedex 75Evaporative Light Scattering Detector (Sedere, Alfortville Cedex,France). A Waters symmetry column (Waters Symmetry® (Trademark byWaters) C18, 3.5 μm, 2.1 mm×150 mm, Waters GmbH, Eschborn, Germany) wasused as stationary phase with a flow rate of 0.4 ml/min at 40° C. Mobilephase A: 0.1% formic acid in water, mobile phase B: 0.1% formic acid inacetonitrile; gradient: 0-1 min. 98% A, from 1-21 min. to 100% B, from21-27 min 100% B. The UVN is spectra were recorded between 200-500 nm,the LC-MS (Liquid Chromatography-Mass Spectrometry coupling) spectrawere recorded in the range of molecular weights between 160 and 1.600Da.

b) “Adapted Method”

LC-MS/UVELSD analyses were performed using an Agilent HP1100 (Agilent,Waldbronn, Germany) liquid chromatograph coupled with a LCT massspectrometer (Waters Corporation, Milford, Mass., USA) in the positiveand negative electrospray ionization (ESI) mode and a Sedex 75Evaporative Light Scattering Detector (Sedere, Alfortville Cedex,France). A Waters symmetry column (Waters Symmetry® (Trademark byWaters) C18, 3.5 μm, 2.1 mm×150 mm, Waters GmbH, Eschborn, Germany) wasused as stationary phase with a flow rate of 0.4 ml/min at 40° C. Mobilephase A: 0.1% formic acid in water, mobile phase B: 0.1% formic acid inacetonitrile; gradient: 0 min: 55% A, from 0-14 min. to 100% B, from14-16 min 100% B. The UV/Vis spectra were recorded between 200-500 nm,the LC-MS (Liquid Chromatography-Mass Spectrometry coupling) spectrawere recorded in the range of molecular weights between 160 and 1.600Da.

c) “Fermentation Control”

HPLC system: Agilent 1100 analytical HPLC system including pumps andautosampler, DAD (200-500 nm) and ELSD detectors; column oven at 40° C.;column: Waters Symmetry® C18 3.5 μm (2.1×150 mm); solvents: deionisedwater (A) and acetonitrile (B) with 0.1% formic acid each. The flow wasadjusted to 0.4 ml/min by using a temperature of 40° C. The gradientapplied was optimized for separation and resolution of the glycolipidpattern: 0 to 14 min: from 45% to 100% (B); 14 to 16 min: 100% (B); 16to 16.1 min: from 100% to 45% (B); 16.1 to 20 min: 45% (B). For HPLCanalysis, samples were dissolved in 2-propanol.

B HPLC-MS of Pure Compounds

TABLE 15 Retention times and MS signals for compounds of the formula I,HPLC prepared according to the methods specified in Section A of thisExample.. HPLC HPLC Compound “Standard “Adapted No. method” method” m/z[16] 14.09 2.94 [M + H]⁺ 887; [M acid]^(·) 459 [14] 14.93 4.73 [M + H]⁺929; [M acid]^(·) 459  [6] 15.15 4.99 [M + H]⁺ 971; [M acid]^(·) 459[17] 15.39 5.55 [M + H]⁺ 901; [M acid]^(·) 473  [7] 15.44 5.68 [M + H]⁺971; [M acid]^(·) 459 [12] 15.79 6.07 [M + H]⁺ 971; [M acid]^(·) 459 [3] 16.32 6.84 [M + H]⁺ 1013; [M acid]^(·) 459 [13] 16.52 7.06 [M + H]⁺1013; [M acid]^(·) 459  [1] 17.00 7.48 [M + H]⁺ 1013; [M acid]^(·) 459 [4] 17.50 8.38 [M + H]⁺ 1054; [M acid]^(·) 459 [10] 17.67 8.50 [M + H]⁺955; [M acid]^(·) 443 [18] 19.36 10.43 [M + H]⁺ 997; [M acid]^(·) 443

C Characterization of Extracts

a) Extract of Ditiola pezizaeformis Strain ATCC13299

TABLE 16 HPLC-MS analysis of an extract obtained from Ditiolapezizaeformis strain ATCC13299 (HPLC-ELSD chromatogram presented in FIG.3) HPLC Compound “Adapted Peak No. method” m/z 1 3.55 [M + H]⁺ 943; [Macid]^(·) 431 2 4.80 [M + H]⁺ 985; [M acid]^(·) 431 3  [7] 5.63 [M + H]⁺971; [M acid]^(·) 459 4 5.83 [M + H]⁺ 985; [M acid]^(·) 431 5 [12] 6.08[M + H]⁺ 971; [M acid]^(·) 459 6 6.67 [M + H]⁺ 927; [M acid]^(·) 415 7 [1] 7.49 [M + H]⁺ 1013; [M acid]^(·) 459 8 7.90 [M + H]⁺ 969; [Macid]^(·) 415 9 8.64 [M + H]⁺ 969; [M acid]^(·) 415 10 8.86 [M + H]⁺969; [M acid]^(·) 415 11 9.58 [M + H]⁺ 983; [M acid]^(·) 429 12 [18]10.51 [M + H]⁺ 997; [M acid]^(·) 443

All shown signals were unequivocally assigned to be glycolipids byHPLC-MS/UV.

b) Extracts of Dacryopinax spathularia Strain MUCL53181Extract [X1]: Glycolipid mixture prepared according to Example 1 from 30l fermentationExtract [X2]: Glycolipid mixture prepared according to Example 1 from200 l fermentation

TABLE 17 HPLC-MS analysis (using the “Adapted method”) of extractsobtained from Dacryopinax spathularia strain MUCL 53181 (HPLC-ELSDchromatogram for [X2] is presented in FIG. 2) Ret. Nominal time MWIdentified compound [min] [Da] class [X1] [X2] 3.8 942 Glycolipidderivative * 0.4 4.3 928 Glycolipid derivative * 0.3 4.6 928 [14] * 0.44.9 984 Glycolipid derivative 0.3 5.1 970 [6] 0.9 1.3 5.6 970 [7] 72.5 25.1  6.1 970 [12] 8.3 12.3  6.5 998 Glycolipid derivative * 0.7 6.61012 Glycolipid derivative 0.9 * 6.8 1012 [3] * 10.8  7.0 998 Glycolipidderivative * * 7.1 1012 [13] 2.6 10.7  7.5 1012 [1] 7.8 29.8  7.8 1012Glycolipid derivative 1.3 4.3 8.4 1054 [4] * 8.5 954 [10] 5.2 2.2 8.8954 + 1054 Glycolipid derivatives * 0.3 8.9 954 Glycolipidderivative * * 9.8 982 Glycolipid derivative * 0.4 10.0 996 Glycolipidderivative * 0.5 10.4 996 [18] 0.4 0.6 11.3 1038 Glycolipidderivative * * Peak area below detection limit of ELSD, but compound wasdetected by ESI MS signals.

Example 4 Biological Activities A. Determination of Minimal InhibitionConcentration a) Non-Pathogenic Microorganisms

Various nonpathogenic bacteria, yeasts, and filamentous fungi wereobtained from public culture collections and maintained as recommendedin the catalogues and protocols of the respective institutions.Saccharomyces cerevisiae strain HT10 and Mucor plumbeus were originallytaken from the culture collection of InterMed Discovery GmbH butdeposited with MUCL as reference strains for antimicrobialsusceptibility testing. These strains were maintained under liquidnitrogen and, prior to the screening, on YMG agar.

Prior to the screening the yeast and bacterial strains were grown overnight on SDB (medium 1), except for Bacillus subtilis, which was grownon YMG agar (medium 2) for 1 week to prepare spore suspensions.Likewise, the filamentous fungi were pre-incubated on YMG agar for 2-3weeks to create inoculum for spore suspensions. The spores were thenrinsed from the surface of the flasks using 0.9% saline, checked forviability by microscopic control and by plating on agar plates, anddiluted to the desired concentration of spores. For all experiments,freshly prepared spore suspensions were used. The initial concentrationsfor the bioassays were adjusted to 1×10⁵ CFU (i.e. cells or spores,respectively) per ml. Standards (preservative agents benzoic acid andsorbic acid; antibiotics: penicillin G, streptomycin sulphate,amphopthericin B) served as positive controls.

To adjust the initial titer prior to the bioassays, the CFU per ml wasdetermined under the microscope using a counting chamber type “BrandNeubauer improved”; BRAND GmbH & Co KG, Wertheim, Germany). Thismicroscopic control also served as means for assessment of the viabilityof the cells.

The actual assays were carried out in Greiner type Bio-one suspensionculture plates (96 Well flat-bottom sterile, No 655185).

The compounds or extracts to be tested from stock material, includingstandards, were dissolved in appropriate volumes of DMSO prior to thetest and diluted into the microtiter plates, using a final concentrationof 1.5%. Aside from regular incubation time for determination of MIC(18-24 h), the stability of the inhibitory effects was also studied atprolonged incubation times. For this purpose, each microtiter plate vialwas filled with 200 μl of the cell suspensions and the test plates wereincubated in an incubator (Heraeus HERA cell) at 28° C. an absolutehumidity of 95%, to prevent evaporation of the solvent. Under suchconditions, no notable evaporation of the microtiter plates was observedfor up to several weeks. MICs were generally determined in a traditionalmanner, by checking the MTP optically and determining the dilution ofeach individual compound where no visible growth had occurred. However,the OD₆₃₀ was also determined using a plate reader, in those cases whereit appeared difficult to observe the MIC with the naked eye. In someinstances, the OD₆₃₀ of the plates could be monitored and determinedusing the plate reader for up to four weeks. However, in general, thelong term experiments were run for at least 168 hours. For determinationof OD₆₃₀, the microtiter plates were scanned using a SPECTROstar Omega(BMG LABTECH, Offenburg, Germany) plate reader, except for thefilamentous fungi, where a PHERAstar plus (BMG LABTECH, Offenburg,Germany) plate reader was used in “Wellscan” mode (orbital averaging at4 mm), since this instrument provided more reliable data if mycelialcolonies had arisen from the initial spore suspensions. MIC in theoptical readout was determined using the following formula:

${{Inhibition}\mspace{14mu}\lbrack\%\rbrack} = {100 - \left( \frac{\left( {\overset{\_}{x}{{OD}_{630}\lbrack{sample}\rbrack}} \right) \times 100}{\left( {\overset{\_}{x}{{OD}_{630}\lbrack{control}\rbrack}} \right)} \right)}$

The MIC values reported relate to the concentration causing at least 80%inhibition as compared to the positive control.

Results:

TABLE 18 MIC values of standards in different media: sorbic acid [SA]and benzoic acid [BA] [SA] [SA] [BA] [BA] day SDB applejuice SDBapplejuice Bacteria B. subtilis 2 250 250 (ATCC6633) 7 250 250 16 250250 28 500 250 L. plantarum 2 >1000 31.3 >1000 250 (DSM12028) 7 >1000500 >1000 >1000 16 >1000 >1000 28 >1000 >1000 L welshimeri 2 500 500 7500 500 16 250 250 28 500 250 Filamentous fungi A. niger 2 250 500(ATCC16404) 7 1000 >1000 16 1000 >1000 28 1000 >1000 M. plumbeus 2 2501000 (MUCL49355) 7 500 1000 16 1000 >1000 28 1000 >1000 Yeast D.bruxellensis 2 500 250 500 125 (DSM70726) 7 500 500 1000 125 16 >1000500 >1000 250 28 >1000 >1000 D. naardenensis 2 250 500 (DSM70743) 7 500500 16 500 500 28 500 500 B. fulva 2 62.5 62.5 (DSM62097) 7 500 500 16500 500 28 500 500 Z. bailii 2 500 >1000 (DSM70492) 7 1000 >100016 >1000 >1000 28 >1000 >1000

TABLE 19 SDB medium: pure compounds day [1] [12] [13] [6] [16] [18] [10][14] Bacteria B. subtilis (ATCC6633) 2 3.1 3.1 3.1 1.6 3.1 3.1 <0.8 73.1 3.1 3.1 1.6 3.1 3.1 <0.8 16 6.3 6.3 3.1 6.3 3.1 3.1 <0.8 28 6.3 6.33.1 6.3 6.3 3.1 <0.8 Filamentous fungi A. niger (ATCC16404) 2 6.3 6.36.3 12.5 3.1 3.1 50 7 12.5 12.5 12.5 25 >100 6.3 50 16 12.5 12.5 62.525 >100 6.3 28 12.5 >100 25 12.5 50 >100 6.3 M. plumbeus (MUCL49355) 2550 12.5 25 >100 25 12.5 50 50 100 25 25 >100 >100 50 >100 Yeast D.bruxellensis (DSM70726) 2 12.5 12.5 6.3 25 >100 3.1 3.1 7 25 25 12.525 >100 12.5 6.3 16 25 25 12.5 50 >100 100 6.3 28 25 25 25 50 >100 1006.3 D. naardenensis 2 (DSM70743) 12.5 100 12.5 25 50 3.1 3.1 25 7 2512.5 25 >100 50 6.3 100 1 25 50 12.5 25 >100 >100 6.3 28 25 >100 12.525 >100 >100 6.3 B. fulva (DSM62097) 2 3.1 6.3 3.1 3.1 6.3 1.6 1.6 7 6.312.5 3.1 6.3 6.3 1.6 1.6 16 6.3 12.5 3.1 6.3 6.3 1.6 1.6 28 31.3 12.515.6 6.3 31.3 7.8 1.6 Z. bailii (DSM70492) 2 25 >100 12.5 25 >100 >1006.3 7 25 >100 12.5 25 >100 >100 12.5 16 12.5 >100 12.5 25 >100 >100 12.528 25 >100 12.5 25 >100 >100 12.5

TABLE 20 SDB medium: extracts day [X1] [X2] [X3] [X4] [X5] [X6] BacteriaB. subtilis 2 <3.9 <3.9 <3.9 >500 7.8 <3.9 (ATCC6633) 7 <3.9 <3.9<3.9 >500 7.8 <3.9 16 <3.9 <3.9 <3.9 <3.9 15.6 <3.9 28 <3.9 <3.9 <3.9<3.9 31.3 7.8 Filamentous fungi A. niger 2 <3.9 <3.9 <3.9 <3.9 125 <3.9(ATCC16404) 7 7.8 7.8 7.8 15.6 500 7.8 16 7.8 7.8 7.8 7.8 >500 7.8 287.8 7.8 7.8 15.6 >500 7.8 M. plumbeus 2 7.8 7.8 7.8 15.6 62.5 7.8(MUCL49355) 7 15.6 15.6 15.6 31.3 125 15.6 16 15.6 31.3 31.3 31.3 >50031.3 28 62.5 31.3 62.5 125 >500 250 Yeast D. naardenensis 2 7.8 <3.9 7.87.8 125 7.8 (DSM70743) 7 7.8 7.8 15.6 15.6 500 15.6 16 7.8 7.8 15.615.6 >500 31.3 28 7.8 15.6 15.6 15.6 >500 15.6 B. fulva 2 <3.9 <3.9 <3.9<3.9 15.6 <3.9 (DSM62097) 7 <3.9 <3.9 <3.9 <3.9 62.5 <3.9 16 <3.9 <3.9<3.9 <3.9 62.5 <3.9 28 <3.9 <3.9 <3.9 <3.9 62.5 <3.9

TABLE 21 SDB vs apple juice medium: pure compounds and extracts day [1][13] [6] [10] [X1] [X2] [X3] [X4] [X5] [X6] Bacteria L. plantarum 2(DSM12028) 12.5 6.3 25 3.1 >100 <3.9 7.8 <3.9 250 >500 SDB 7 25 12.5 256.3 >100 <3.9 15.6 500 7.8 16 25 12.5 50 6.3 15.5 <3.9 31.3 <3.9 >5007.8 28 25 6.3 25 6.3 15.6 31.3 31.3 <3.9 >500 7.8 L. plantarum 2(DSM12028) 6.3 <0.8 6.3 <0.8 <3.9 <3.9 <3.9 <3.9 62.5 <3.9 apple juice7 >100 <0.8 50 <0.8 62.5 >500 <3.9 >500 259 125 Yeast Z. bailii(DSM70492) 2 25 12.5 25 6.3 7.8 7.8 7.8 15.6 125 >500 SDB 7 25 12.5 2512.5 7.8 7.8 7.8 15.6 125 >500 16 12.5 12.5 25 12.5 7.8 7.8 7.8 15.6 25015.6 28 25 12.5 25 12.5 15.6 7.8 7.8 15.6 250 15.6 Z. bailii (DSM70492)2 6.3 3.1 3.1 3.1 <3.9 <3.9 >500 <3.9 31.3 <3.9 apple juice 7 6.3 3.16.3 <3.9 <3.9 >500 <3.9 31.3 <3.9 16 6.3 3.1 3.1 3.1 <3.9 <3.9 <3.9 <3.931.3 <3.9 28 6.3 3.1 3.1 3.1 <3.9 <3.9 <3.9 <3.9 31.3 <3.9 D.bruxellensis 2 (DSM70726) 12.5 6.3 25 3.1 7.8 <3.9 7.8 7.8 250 7.8 SDB 725 12.5 25 6.3 15.6 7.8 15.6 31.3 >500 15.6 16 25 12.5 50 6.3 15.6 7.815.6 15.6 >500 31.3 28 25 12.5 25 6.3 15.6 15.6 15.6 31.3 >500 31.3 D.bruxellensis 2 (DSM70726) 6.3 3.1 3.1 3.1 <3.9 <3.9 <3.9 <3.9 15.6 <3.9apple juice 7 25 6.3 3.1 3.1 <3.9 <3.9 <3.9 <3.9 31.3 <3.9 16 6.3 6.33.1 3.1 <3.9 <3.9 <3.9 <3.9 31.3 <3.9 28 6.3 3.1 3.1 3.1 <3.9 <3.9 <3.9<3.9 31.3 <3.9 Note: Apple juice medium per se shows already limitedgrowth which is based mainly on the low concentration of nitrogencompounds available and needed for growth.

It is evident and remarkable that independently of the extraction method(e.g. X1-X3) comparable results are achieved.

Bacteria

Bacillus subtilis (ATCC6633)Clostridium perfringens (ATCC13124)Corynebacterium variabile (DSM20132)Corynebacterium variabile (ATCC15753)Escherichia coli (ATCC9637)Lactobacillus plantarum (DSM12028)Pseudomonas putida (ATCC17484)Staphylococcus aureus (ATCC 6538P)

Filamentous Fungi (<<Molds>>)

Aspergillus fumigatus (ATCC1028)Aspergillus niger (ATCC16404)Byssochlamys fulva (DSM62097)Mucor plumbeus (MUCL49355)

Yeasts

Dekkera bruxellensis (DSM70726)Dekkera naardenensis (DSM70743)Saccharomyces cerevisiae (HT10)Zygosaccharomyces bailii (DSM70492)Zygosaccharomyces bailii (ATCC60484)Zygosaccharomyces bisporus (DSM70415)Zygosaccharomyces florentinus (DSM70506)Zygosaccharomyces rouxii (NCYC381)

b) Pathogenic Microorganisms

Several samples of extracts and pure compounds were tested againstStaphylococcus aureus (ATCC 6538P), Clostridium perfringens (ATCC 13124)or Aspergillus fumigatus (ATCC 1028). The test was performed by RicercaBiosciences, LLC (Taiwan): S. aureus (cat no 604000) with Mueller-HintonBroth medium using 1% DMSO as vehicle for an incubation time of 20 hoursat 36° C. (di Modugno, Antimicrob Agents Chemother (1994) 38: 2362-8);C. perfringens (cat no 620700) with Reinforced Clostridial Medium using1% DMSO as vehicle for an incubation time of 2 days at 36° C. (diModugno, ibid); A. fumigatus (cat no 640010) with Potato Dextrose Brothmedium using 1% DMSO as vehicle for an incubation time of 3 days at 28°C. (Turner, Antimicrob Agents Chemother (1989) 33(2): 215-22). MICs weredetected via turbidity measurements in all cases.

The average mol weight was set to 1000 g/mol, the presented data in thefollowing table 22 are given in mg/ml (ppm).

TABLE 22 MICs [ppm] of extracts and pure compounds against humanpathogenic microorganisms. S. aureus C. perfringens A. fumigatus D.spathularia MUCL 60 20 53181 extract D. spathularia MUCL 60 60 53182extract  [1] 200 60 20 [12] 200 60 20

Example 5 Sensory Evaluation

The extract [X2] was dissolved in water to final concentrations of 10ppm and 100 ppm. These two test samples were presented together with apure water sample (as negative control) to two test persons. The threesamples were blinded prior to the taste evaluation.

None of the test persons were able to discriminate between pure waterand the sample containing 10 ppm of the test compound. The samplecontaining 100 ppm of the test compound was described with a diffusetaste comparable with water which was stored for a longer time in anopen PET bottle. No bitter, spicy or otherwise unpleasant taste wasobserved.

In a second trial one test person tried the pure dry powder of the abovetest compound. Even after this application no further adverse orunpleasant taste was named.

Example 6 Optical Rotation Values

Optical rotation values were determined in methanolic solutions using aSchmidt-Haensch, Unipol L 1000 polarimeter equipped with a silica glassmicro cuvette (100 mm length; 1 ml sample volume).

TABLE 23 Specific optical rotation values in methanol Compound/ extractalpha^(D) ₂₀ c [g/100 mL]  [1] −20.0 0.34 [13] −22.3 0.36 [16] +23.50.22 [17] n.d. [12] −19.1 0.93 [14] n.d. [10] −18.8 0.52 [18] −23.0 0.95 [7] n.d.  [6] −29.4 0.64 [X2]  −25.5 0.68

Example 6 Apple Juice Based Beverage

(cf. WO 2010/148045)

A 2% fruit juice based non-carbonated beverage of pH 3.4 and about 12Brix is formed by combining the following ingredients.

Ingredient % Composition Water ca. 84 (added to final 100%) Apple juiceconcentrate 0.372 of concentrate to provide single strengthconcentration of about 2% Sucrose 6.8 Glucose 5.2 Fructose 0.2 Compoundextract [X2] 0.000001-0.5% Malic acid 0.134 Sodium malate 0.013CaCl2—2H2O 0.011 MgCl2—6 H2O 0.003 EDTA 0.003

A pH of 3.4 is achieved through combinations of malic acid and sodiummalate. The total combined quantity of sodium malate and malic acid isnear constant, but the ratio of malic acid and malate varied slightlydepending on the content of compound extract [X2].

The above mixture is inoculated with test organisms and incubated forweeks at ambient temperature.

Example 7 Semifinished Products

A) The following mixtures can be used as concentrates for preservativeefforts in different foods or beverages.

Compound Concentration in % Variation A B C Water ca. 70 ca. 84 ca. 50Sucrose, acetate 2 5 isobutyrate Xanthan gum 0.16 Gum arab 6 4 Beeswax 1TWEEN 20 5 Ethanol 10 Glycerol 5 Citric acid 5 Orange oil 5 Compound[X2] 0.1 0.1 0.1

Compound extract [X2] is used as concentrated solution (concentrate) inDMSO which will be diluted to a final DMSO content of (concentrate) inthe semi finished products. The compound extract [X2] solution ispremixed with the appropriate alcohol, in variation C together with theorange oil, in variation B together with the beeswax, whereas thethickeners are mixed with an appropriate volume of water. The twomixtures are vigorously stirred, combined by continuing the stirring andfilled up with water to the final volume (100%).

B) The following mixture is to be used as concentrate for an apple juicebeverage (9 liter)

Ingredients Amount Sucrose 10% Clear juice (apple) 10% Flavor emulsion(variant C 0.2%  of the above table) Citric acid 0.15%  Water ca. 7.2 I

The semifinished products are tested against microorganisms e.g. mold,yeasts and/or bacteria.

Example 8 Production and Isolation of a Mixture of Compounds of FormulaI and a Mixture of Sodium Salts of Compounds of Formula I

A) Fermentation Using the Strain FU50088 (Dacryopinax spathularia StrainMUCL 53181)

a) Seed Cultures (Shake Flask Cultures)

One ml of a cryo vial containing a mycelial suspension of strain MUCL53181 in 10% glycerol was retrieved from liquid nitrogen and, afterthawing, used to inoculate 200 ml Erlenmeyer flasks containing 50 ml ofsterile YMG medium and propagated on a rotary shaker at 240 rpm and 23°C. for 72 h. Thereafter, each two ml of the primary seed culture weretransferred into batches of two 500 ml Erlenmeyer flasks containing 200ml of the same medium and propagated on a rotary shaker at 140 rpm and28° C. for 90 h. These flasks served as secondary seed cultures.

b) Fermentation in 301 Scale

A 40 l Biostat LP42 fermentor (Bioengineering, Wald, Switzerland)containing 301 of GM2 medium was sterilized in situ (1 h at 121° C. and1.1 bar) and inoculated with 1500 ml of the secondary seed culture. Theproduction culture was grown under stirring (240 rpm) and aeration (0.2vvm (volumes of air per minute per volume of batch) at 30° C. for 200 h.

B) Downstream Processing and Isolation B-1) Isolation of a Mixture ofCompounds of Formula I

The culture broth resulting from the 301 fermentation of Example 8A) b)was alkalized from an initial pH value of 4.5 to a pH value of 8 with 5N sodium hydroxide solution to allow the glycolipids that partiallystick to the cells under acidic conditions to become largely releasedfrom the mycelia. After 1 h the mycelia were separated from the culturebroth by centrifugation, and then the culture broth was filtratedadditionally through a Pall T1000 depth filter (Dreieich, Germany) toremove cell clusters and filamentous material. The product wassedimented (precipitated) by acidifying the filtrate with 6 Nhydrochloric acid to pH 2.2 and subsequent storing for 20 h at 4° C. Thefluid was removed by decantation, subsequent centrifugation (4500 rpm,15 min, Type Jouan SA LR 5.22 (Jouan, Paris, France) and then discarded,resulting in a whitish-grey gel. This crude product was washedimmediately with 11 of slightly basic demineralized water (set to apH-value of 8 with sodium hydroxide) and centrifuged at (4500 rpm for 15min). The supernatant was removed and the remaining pellet suspended in0.5 l demineralized water. After decantation the residue wasfreeze-dried to yield a slightly beige-grey powder (residual watercontent: 1.36% (according to the Karl Fischer method), the total proteincontent was below 1% (<1%) (Kjeldahl method according to ISO 5549:1978). This process yielded a total of 87 g of glycolipids whichsubsequently were characterized by HPLC-MS (see [X7] in Table 24).

B-2) Isolation of a Mixture of Sodium Salts of Compounds of Formula I

The culture broth resulting from the 301 fermentation of Example 8A) b)was alkalized from an initial pH value of 4.5 to a pH value of 8 with 5N sodium hydroxide solution to allow the glycolipids that partiallystick to the cells under acidic conditions to become largely releasedfrom the mycelia. After 1 h the mycelia were separated from the culturebroth in a separator, and then the culture broth was pumped through acombined filter assembly: first though a depth filter with a pore sizeof 0.65 μm and then through a membrane filter with a pore size of 0.45μm to remove not only filamentous material and cell clusters but alsocells. The product was sedimented (precipitated) by acidifying thefiltrate with 6 N hydrochloric acid to pH 2 and then stored for 16 h at4° C. The fluid was removed by decantation, subsequent centrifugation(4500 rpm, 15 min, Type Jouan SA LR 5.22 (Jouan, Paris, France) and thendiscarded, resulting in a whitish-grey gel. This crude product waswashed immediately with 1 l demineralized water and centrifuged at (4500rpm for 15 min). The supernatant was removed, the remainder suspended in0.5 l demineralized water and the pH adjusted to a pH value of about 6with 5 N sodium hydroxide solution. Finally, the resulting solution wasfreeze-dried to yield a total of 93 g of sodium salts of glycolipids indry form as a slightly beige powder (residual water content: 1.2%(according to the Karl Fischer method), the total protein content wasbelow 1% (<1%) (Kjeldahl method according to ISO 5549: 1978).

C) HPLC-MS Analysis—“Improved Method”

HPLC-MS analyses were performed using a Dionex Ultimate® 3000 RSLC(Thermo Fisher GmbH, Idstein; Germany) liquid chromatograph coupled witha amaZon SL ion trap mass spectrometer (Bruker Daltonik GmbH, Bremen,Germany) in the negative electrospray ionization (ESI) mode and a Sedex85 ELSD (Sedere, Alfortville Cedex, France). A Nucleoshell RP18 column(2.7 μm, 2 mm×150 mm, Macherey-Nagel GmbH & Co. KG, Düren, Germany) wasused as stationary phase with a flow rate of 0.4 ml/min at 40° C. Mobilephase A: 0.1% formic acid in water, mobile phase B: 0.1% formic acid inacetonitrile; gradient: 0 min: 70% A, from 0-40 min. to 40% A, from40-42 min to 0% A, from 42-48 min. 0% A, from 48-49 min to 70% A, from49-55 min 70% A. The LC-MS (Liquid Chromatography-Mass Spectrometrycoupling) spectra were recorded in the range of molecular weightsbetween 700 and 1.200 Da.

TABLE 24 HPLC-MS analysis (using the “Improved method”) of the extract[X7] obtained from Dacryopinax spathularia strain MUCL 53181 accordingto Example 8 B-1) Ret. Molecular time weight [X7]* [min] [Da] Identifiedcompound (type) in wt. % 13.49 886 [16]  0.1 14.20 886 Glycolipidwithout acyl groups 0.1 14.46 942 Glycolipid 1.6 15.46 928 Glycolipid0.4 15.79 928 Glycolipid 1.2 16.27 928 Glycolipid 0.2 16.55 928Glycolipid 1.2 16.98 928; 956 Glycolipids 1.1 17.38 928 [14]  0.8 17.49970 Glycolipid 0.2 17.78 970 Glycolipid 0.9 18.26 970 Glycolipid 1.618.58 970 Glycolipid 0.5 19.00 970 [6] 2.3 19.73 970 Glycolipid 16.919.98 970 [7] 22.6 20.66 970; 984 Glycolipids 1.1 20.90 970 Glycolipid3.4 21.44 970 Glycolipid 2.3 21.69 970 [12]  2.8 22.02 984 Glycolipid0.3 22.57 970; 998 Glycolipids 1.3 22.86 926; 998 Glycolipids 1.2 23.091012 Glycolipid 1.0 23.91 1012 [5] 1.1 24.02 1012 [9] 2.4 24.19 1012Glycolipid 0.4 24.73 1012 [13]  1.0 25.00 1012 Glycolipid 4.0 25.96 1012[8] 1.9 26.22 1012 [1] 6.7 26.34 1012 Glycolipid 3.0 27.18  954; 1012Glycolipids 0.7 27.33 1012 Glycolipid 0.4 27.89 968 Glycolipid 0.4 29.08954 [10]  5.4 29.51 954; 968; 1054 Glycolipids 0.9 29.81 1054 [4] 1.630.52 954 Glycolipid 0.3 30.93 1054 Glycolipid 0.3 33.65 982 Glycolipid0.5 34.46 996 Glycolipid 1.1 36.04 996 [18]  1.5 43.86 No Glycolipid 1.1*Some minor peaks of [X7] are not listed in Table 24.

D) Fermentation in 400 Ml Scale

A 1 l Erlenmeyer flask containing 400 ml of sterilized medium (2.0%D-glucose, 0.5% malt extract) was inoculated with 2 ml of the secondaryseed culture from Example 8A a). The production culture was grown on arotary shaker at (200 rpm) at 32° C. for 360 h.

Work-up after 360 h of fermentation yielded a total of 5.6 g/l ofglycolipids of formula I which subsequently were characterized byHPLC-MS (see [X8] in Table 24A).

TABLE 24A HPLC-MS analysis (using the “Improved method” of Example 8 C))of the extract [X8] obtained from Dacryopinax spathularia strain MUCL53181 according to Example 8 D) (the HPLC-ESI chromatogram for [X8] ispresented in FIG. 4) Ret. Molecular time weight [X8]* [min] [Da]Identified compound (type) in wt. % 13.08 886 Glycolipid without acylgroups 0.4 13.49 886 [16]  0.5 14.20 886 Glycolipid without acyl groups0.4 14.46 942 Glycolipid 0.6 15.46 928 Glycolipid 0.5 15.79 928Glycolipid 1.0 16.27 928 Glycolipid 0.2 16.55 928 Glycolipid 1.6 16.98928; 956 Glycolipids 1.0 17.38 928 [14]  0.1 17.49 970 Glycolipid 1.417.78 970 Glycolipid 1.9 18.26 970 Glycolipid 0.3 18.58 970 Glycolipid1.5 19.00 970 [6] 1.9 19.73 970 Glycolipid 12.7 19.98 970 [7] 12.4 20.66970; 984 Glycolipids 1.4 20.90 970 Glycolipid 5.5 20.99 870 Glycolipidwithout acyl groups 1.5 21.44 970 Glycolipid 2.1 21.69 970 [12]  3.022.02 984 Glycolipid 0.4 22.57 970; 998 Glycolipids 2.9 23.09 1012Glycolipid 0.9 23.91 1012 [5] 1.7 24.02 1012 [9] 2.8 24.19 1012Glycolipid 0.8 24.73 1012 [13]  1.2 25.00 1012 Glycolipid 4.6 25.96 1012[8] 2.1 26.22 1012 [1] 8.8 26.34 1012 Glycolipid 3.6 27.18  954; 1012Glycolipids 1.3 27.33 1012 Glycolipid 4.4 27.89 968 Glycolipid 0.5 29.08954 [10]  4.7 29.51 954; 968; 1054 Glycolipids 1.1 29.81 1054 [4] 0.230.52 954 Glycolipid 0.6 30.93 1054 Glycolipid 0.6 33.65 982 Glycolipid0.6 34.46 996 Glycolipid 0.7 36.04 996 [18]  2.2 43.86 No Glycolipid 1.0*Some minor peaks of [X8] are not listed in Table 24A.

E) Fermentation in 400 ml Scale

A 1 l Erlenmeyer flask containing 400 ml of sterilized medium (4.0%D-glucose, 0.2% yeast extract) was inoculated with 6 ml of the secondaryseed culture from Example 8A a). The production culture was grown on arotary shaker at (200 rpm) at 32° C. for 240 h.

Work-up after 240 h of fermentation yielded a total of 6.2 g/l ofglycolipids of formula I.

Example 9 Biological Activities

In analogy to the methods described in Example 4 above, furtherbiological activity MIC data were determined for several pure (purity>94wt. %) compounds and for the mixture of compounds of formula I (extract[X8] as described in detail in Example 8D).

The following Tables 25-27 represent the corresponding MIC values ofseveral pure compounds after 48 h against various microorganisms.

In summary, Tables 25-27 demonstrate that individual compounds offormula I without any acyl substituents in the trisaccharidecarbohydrate moiety R (such as the case for compound [16]) typicallyexhibit a significantly weaker antimicrobial activity, particularlyagainst yeasts and molds, than the corresponding compounds being mono-or diacylated in the saccharide moiety.

Said Tables also demonstrate that individual compounds of formula I withan acyl substituent with more than 2 carbon atoms, such as an isovalerylsubstituent, in the trisaccharide carbohydrate moiety R (such as thecase for compounds [12], [13] and [1]) typically exhibit a strongerantimicrobial activity, particularly against yeasts and molds, and/or abroader activity spectrum than the corresponding compounds with oneacetyl substituent in the trisaccharide carbohydrate moiety R (such ascompound [14]).

TABLE 25 MIC values [ppm] after 48 h of pure compounds againstGram-positive bacteria Bacteria [16] [14] [12] [13] [1] Bacillussubtilis (ATCC6633) 3.1 1.6 1.6 3.1 3.1 Propionibacterium acnes 100(ATCC6919) Clostridium perfringens 60 60 (ATCC13124) Corynebacteriumvariabile 1.6 1.6 <0.8 1.6 1.6 (DSM20132) Lactobacillus plantarum 50 2525 25 25 (DSM12028)

TABLE 26 MIC values [ppm] after 48 h of pure compounds againstfilamentous fungi (molds) Filamentous fungi [16] [14] [12] [13] [1]Aspergillus fumigatus 20 20 (ATCC1028) Aspergillus niger (ATCC16404) 2550 6.3 12.5 3.1 Byssochlamys fulva (DSM62097) 6.3 6.3 3.1 3.1 Mucorplumbeus (MUCL49355) >100 50 6.3 12.5 6.3 Talaromyces luteus (CBS348.51)50 50 25 25 12.5 Pyricularia oryzae (DSM62938) 25 25 25 6 6 Dekkerabruxellensis >100 50 6.3 6.3 6.3 (DSM70726) Dekkera naardenensis 50 256.3 12.5 6.3 (DSM70743)

TABLE 27 MIC values [ppm] after 48 h of pure compounds against yeastsYeasts [16] [14] [12] [13] [1] Saccharomyces cerevisiae (HT10) >100 506.3 12.5 6.3 Zygosaccharomyces bailii 25 25 6.3 6.3 6.3 (DSM70492)Zygosaccharomyces bisporus >100 50 12.5 25 12.5 (DSM70415)Zygosaccharomyces florentinus >100 50 6.3 12.5 6.3 (DSM70506)Zygosaccharomyces rouxii 100 25 6.3 12.5 6.3 (NCYC381) Candida albicans(ATCC10231) 30

The following Table 28 represents the MIC values [ppm] of mixture [X8]and pure compound [12] after 48 h against various microorganisms.

TABLE 28 MIC values [ppm] of mixture [X8] and pure compound [12] after48 h [X8] [12] Bacteria Bacillus cereus (ATCC11778) 12.5 12.5 Bacillussubtilis (ATCC6633) 1.6 Propionibacterium acnes (ATCC6919) 60Clostridium perfringens (ATCC13124) 60 Clostridium sporogenes (ATCC3584)50 50 Enterococcus faecalis (ATCC19433) 50 50 Listeria welshimeri(DSM15452) 25 25 Listeria monocytogenes (ATCC19111) 50 50Corynebacterium variabile (DSM20132) <0.8 Lactobacillus plantarum(DSM12028) 25 Staphylococcus aureus (ATCC6538) 25 Filamentous fungiAspergillus fumigatus (ATCC1028) 20 Aspergillus niger (ATCC16404) 6.3Byssochlamys fulva (DSM62097) 3.1 Mucor plumbeus (MUCL49355) 6.3Talaromyces luteus (CBS348.51) <3.9 Pyricularia oryzae (DSM62938) 6Dekkera bruxellensis (DSM70726) 6.3 Dekkera naardenensis (DSM70743) 12.5Yeasts Saccharomyces cerevisiae (HT10) 12.5 Zygosaccharomyces bailii(DSM70492) 6.3 Zygosaccharomyces bisporus (DSM70415) 12.5Zygosaccharomyces florentinus (DSM70506) 6.3 Zygosaccharomyces rouxii(NCYC381) 6.3 Candida albicans (ATCC10231) 12.5 25 Candida glabrata(ATCC36583) 20

At a concentration of 25 ppm [X8], the observed inhibition of Bacilluscereus was 90%. At a concentration of 12.5 ppm [X8], the observedinhibition of Candida albicans was 90-100%. At a concentration of 50 ppm[X8], the observed inhibition of Clostridium sporogenes was 80-90%. At aconcentration of 100 ppm [X8], the observed inhibition of Staphylococcusaureus was 90%.

The following Table 29 shows the results of several bacteria count testsperformed with mixture [X8] for various microorganisms in comparisonwith an untreated control. Tests were performed at 37° C. at a pH of 7.4in full medium. The respective bacteria count (Ba.C) is indicated incolony forming units/ml (CFU/ml).

TABLE 29 Bacteria count tests performed with mixture [X8] Sample withUntreated Initial [X8] Ba•C control Ba•C Ba.C after after after after[X8] 0 h 2 h 6 h 2 h 6 h Listeria 100 5 × 10⁵ 1 × 10⁴ 1 × 10⁴ 1.1 × 10⁶  5 × 10⁷ monocytogenes ppm (ATCC19111) Staphylococcus 100 1 × 10⁵ 1 ×10⁴ 5 × 10³   5 × 10⁵   1 × 10⁸ aureus ppm (ATCC6538) Enterococcus 200 5× 10⁴ 1 × 10⁴ 1 × 10⁴   5 × 10⁵   1 × 10⁸ faecalis ppm (ATCC19433)Bacillus cereus  50 1 × 10⁵ 1 × 10² <10   2 × 10⁶   7 × 10⁸ (ATCC11778)ppm Micrococcus 500 1 × 10⁸ 2 × 10² 2 × 10¹  >1 × 10⁸  >1 × 10⁹ luteusppm

Example 10 Sugar-Free Beverage Compositions

A B C D Ingredient in wt. % in wt. % in wt. % in wt. % Potassium sorbate— — 0.03  — Sodium benzoate 0.03  — 0.015 — Phosphoric acid 0.048 0.06 0.025 0.16 Citric acid 0.016 0.012 0.025 0.02 Caffeine 0.013 0.009 — —Sucralose — — 0.008  0.0052 Aspartame 0.030 0.018 — — Acesulfame K 0.0095  0.0055 0.019 — Na cyclamate — 0.050 0.045  0.009 Na Saccharin —0.006 0.01  — Erythritol 0.20  — — 0.45 Dimethylpolysiloxane — — 0.00075  0.0008 Lemon-orange flavor — — 0.25  0.15 Cola flavor 0.35 0.42  — 0.20 Caramel color (E150d) 0.009 0.009 —  0.008 Extract [X7] of 0.0003 — —  0.0001 Example 8 B-1) Extract [X8] of —  0.0005  0.0004 —Example 8 D) Pure compound [1] — — —  0.0003 Drinking water Ad 100 Ad100 Ad 100 Ad 100 The beverage compositions A and C each were carbonatedwith 3.8 volumes of carbon dioxide after filling into bottles. Thebeverage compositions B and D each were carbonated with with 3.0 volumesof carbon dioxide after filling into bottles.

The beverage compositions A and C each were carbonated with 3.8 volumesof carbon dioxide after filling into bottles. The beverage compositionsB and D each were carbonated with 3.0 volumes of carbon dioxide afterfilling into bottles.

Example 11 Tea Beverage Compositions

A B C D Ingredient in wt. % in wt. % in wt. % in wt. % Sucrose 3.30 — —— Trisodium citrate 0.50 0.50 0.25 — Citric acid 0.40 0.60 0.50 0.80Malic acid — 0.20 0.30 0.50 Ascorbic acid 0.20 0.10 0.15 0.20 Watersoluble green 2.50 2.25 — — tea powder Water soluble Ceylon — — 2.752.40 black tea powder Sucralose — 0.08 0.05 — Acesulfame K  0.0035 0.0035  0.0045  0.0055 Aspartame — — —  0.025 Rebaudioside A 0.01 — 0.005 — Peach flavor — — 0.40 — Lemon flavor — — — 0.70 Jasmine teaflavor — 0.45 — — Colorant  0.007  0.009  0.009  0.008 Extract [X7] of 0.0003  0.0002 Example 8 B-1) Extract [X8] of —  0.0005  0.0004  0.0003Example 8 D) Drinking water Ad 100 Ad 100 Ad 100 Ad 100

Example 12 Beverage Compositions

A B C D Ingredient in wt. % in wt. % in wt. % in wt. % Sucrose 7.7010.40  6.00 4.00 Erythritol 0.22 — — 0.40 Tagatose 0.44 — — 0.30Trehalose — — 3.00 — Fructose — — 1.00 1.00 Citric acid, anhydrous 0.30 0.235 0.21 0.21 Sodium benzoate — — 0.04 0.05 Potassium sorbate — —0.02 0.03 Ascorbic acid 0.10 0.15 0.10  0.125 Lemon oil, cold pressed0.08 — — — Orange oil, cold pressed 0.02 0.09 0.09 0.09 FD&C Yellow 5 0.003  0.007  0.007  0.007 FD&C blue No. 1  0.006 —  0.002  0.002Rebaudioside A —  0.008 — 0.02 Titanium dioxide — 0.08 — — Extract [X7]of  0.0003 — — — Example 8 B-1) Extract [X8] of —  0.0005  0.0001 0.0003 Example 8 D) Pure compound [1] — —  0.0002 — Tap water Ad 100 Ad100 Ad 100 Ad 100 The beverage compositions A and C each were carbonatedwith 4 volumes of carbon dioxide after filling into bottles. Thebeverage composition B was carbonated with 2 volumes of carbon dioxideafter filling into bottles.

The beverage compositions A and C each were carbonated with 4 volumes ofcarbon dioxide after filling into bottles. The beverage composition Bwas carbonated with 2 volumes of carbon dioxide after filling intobottles.

Example 13 Yogurt Drink Compositions

Skimmed milk and whole milk were mixed in proportions to give milk with1.1% fat, then 5 wt. % of sucrose were added thereto, and heated to 82°C. for 30 minutes. After cooling to 42° C., 0.7% of a commerciallyavailable starter culture of Bifidobacterium bifidum and 0.5% of astarter culture of Streptococcus thermophilus culture were added, andthe mixture cultured at 39° C. until the pH-value of the mixture reached4.4. The resulting firm yoghurt curd was then broken by stirring, andsplit in two portions (portion A and portion B).

Preparation of LiqYog A: To stirred portion A were added 0.4 wt. %(based on the mass of firm yoghurt) of high methoxyl citrus pectin as 5wt. % solution in water and the mixture cooled with stirring to 5° C.This product was then passed through a sterilized homogenizer at 40 barto give a liquid yoghurt having a dynamic viscosity of 380 mPas at 10°C. Thereto were first added with stirring 45 ppm of the extract [X7] ofExample 8B-1), and then 9.0 wt. % of a pasteurized peach pulp, in bothcases based on the total weight of the liquid yoghurt. The resultingmixture was homogenized giving LiqYog A which was transferred into aglass container, and stored at 7° C. for 10 days.

Preparation of LiqYog B: To stirred portion B were added 0.6 wt. %(based on the mass of firm yoghurt) of high methoxyl apple pectin as 5wt. % solution in water and the mixture cooled with stirring to 5° C.This product was then passed through a sterilized homogenizer at 15 barto give a liquid yoghurt having a dynamic viscosity of 600 mPas at 10°C. Thereto were first added with stirring 95 ppm of the extract [X8] ofExample 8D), and then 7.5 wt. % of a pasteurized strawberry-blueberrypuree, in both cases based on the total weight of the liquid yoghurt.The resulting mixture was homogenized giving LiqYog B which was storedat 8° C. before further processing.

Example 14 Mouthwashes

A B C Ingredient in wt. % in wt. % in wt. % Ethanol (96% in water) 8.005.00 — Glycerin 8.00 10.00  12.00  1,2-Propylene Glycol — — 2.00 SodiumFluoride 0.05 0.13 0.10 Poloxamer 407 (Pluronic F-127 ®, 1.40 — 0.60BASF) PEG-40 hydrogenated castor oil and — 1.00 0.50 propylene glycol(Cremophor ® CO 40, BASF) Sodium Phosphate buffer (pH 7.0) 1.10 — 1.00Blue colorant (1% in water) 0.10 0.05 — Red colorant (1% in water) —0.05 0.08 Sorbic acid  0.025 — — Benzoic acid  0.025 — —4-Hydroxybenzoic acid methylester — — 0.06 Na Salt Sodium Saccharinate0.10 — 0.12 Sorbitol (70% in water) — 3.00 — Eucalyptusoil-menthol-wintergreen 0.15 0.10 — flavour Peppermint-spearmint flavour— 0.10 0.20 (menthol content: 58%) Cetylpyridinium Chloride 0.05 — 0.07Hydrogen Peroxide (30% in water) — — 3.00 Extract [X7] of  0.0005 — —Example 8 B-1) Extract [X8] of —  0.001  0.0003 Example 8 D) Purecompound [1] — — 0.0001 Deionized water Ad 100 Ad 100 Ad 100

Example 15 Perfume Oils for Use in Cosmetic Compositions

Perfume oil P1 Perfume oil P2 Ingredient parts by weight parts by weightAcetophenone, 10% in DPG 10.00 — n-Undecanal 15.00  5.00Allylamylglycolate, 20.00 — 10% in DPG Amylsalicylate 25.00 15.00 Benzylacetate 60.00 40.00 Citronellol 80.00 50.00 D-Limonen 60.00 10.00Dihydromyrcenol 60.00 15.00 Eucalyptus oil 10.00 — Geraniol 40.00 60.00Nerol 20.00 20.00 Geranium oil 15.00 15.00 Hexenol cis-3, 10% in DPG 5.00 15.00 Hexenyl salicylate cis-3 20.00 — Indole, 10% in DPG 10.00 —Alpha-Ionone 15.00 15.00 Vanillin  5.00 — Lilial (2-methyl-3-(4-tert-60.00 — butyl-phenyl)propanal) Linalool 40.00 60.00 Methylphenyl acetate10.00 — Phenylethyl alcohol 255.00  30.00 Styrene acetate 20.00 20.00Terpineol 30.00 — Tetrahydrolinalool 50.00 50.00 Cinnamon alcohol 10.00— Ambrettolide — 25.00 p-tert-Butyl cyclohexyl 20.00 80.00 acetateExaltolide — 50.00 Galaxolide, 50% in IPM 30.00 120.00  Hexadecanolide —10.00 Iso E Super 20.00 75.00 Musk indanone — 70.00 Coumarine — 20.00Patchouli oil — 70.00 Vetiveryl acetate — 50.00 Methyl dihydrojasmonate20.00 90.00 DPG = Dipropylene glycol; IPM = Isopropyl myristate

Example 16 Roll-on Deodorant Emulsions

A B C Ingredient in wt. % in wt. % in wt. % PEG-40 Stearate 5.00 4.005.50 Ethylhexylglycerin 1.00 1.20 — (Octoxyglycerin) Cetyl Alcohol 2.001.00 1.70 Stearyl Alcohol — 1.00 0.50 Mineral oil 2.00 2.00 2.00Aluminum Hydrochlorate powder — 8.00 15.00  Polysorbate 80 0.80 1.001.20 Glycerin 2.50 1.50 1.50 Mg-Aluminium Silicate 0.80 0.80 0.80 Talc1.50 — — 1,2-Pentandiol — — 0.60 1,2-Octandiol — 0.75 0.20 2-Benzylheptanol — 0.10 — 2-Methyl-4-phenyl-2-butanol — 0.10 0.304-Methoxybenzyl alcohol 0.10 — — 4-Methyl-4-phenyl-2-pentanol 0.05 —0.10 Extract [X7] of  0.001 —  0.0004 Example 8 B-1) Extract [X8] of — 0.0005  0.0004 Example 8 D) Perfume oil P1 according 0.70 — 0.65 toExample 14 Perfume oil P2 according 0.10 0.60 — to Example 14 Water Ad100 Ad 100 Ad 100

Example 17 Deodorant Microemulsions

A B C Ingredient in wt. % in wt. % in wt. % Glycerin Isostearate 1.802.00 1.80 Octoxyglycerin — 0.80 0.90 Ceteareth-15 5.25 5.50 5.00Isotridecyl Isononanoate 3.30 3.50 3.80 Cyclomethicon 6.80 6.40 6.00L-Menthyl-L-Lactate — 0.20 0.10 Octyldodecanol — 0.40 — AluminiumChlorohydrate — 5.00 9.00 Triclosan ® — — 0.25 Extract [X7] of  0.0012 — 0.0004 Example 8 B-1) Extract [X8] of —  0.0005  0.0006 Example 8 D)Perfume oil P1 according 0.65 0.10 0.45 to Example 14 Perfume oil P2according — 0.40 0.25 to Example 14 Water Ad 100 Ad 100 Ad 100

Example 18 Shampoo Compositions

A B C Ingredient in wt. % in wt. % in wt. % C₁₀₋₃₀ Alkyl acrylatecrosspolymer 0.60 0.60 0.60 Sodium Hydroxide, 15% in water 0.10 0.120.10 Disodium EDTA 0.10 0.10 0.10 1,2-Decandiol 1.00 0.50 1.001,2-Dodecandiol — 0.70 — 1-Tetradecanol — — 0.50 Glycol Distearate,Laureth-4, 3.00 3.00 3.00 Cocamidopropyl Betaine Sodium Laureth Sulfate(SLES), 12.00  14.00  10.00  53% in water Sodium Cocamphoacetate 5.005.00 7.00 Ammonium Cocoyl Isethionate 10.00  8.00 9.00 Acetamide MEA1.00 1.50 0.50 Palmitamide MEA 0.50 — 0.50 Phenoxyethanol — 0.70 0.30Extract [X7] of  0.0015 —  0.0003 Example 8 B-1) Extract [X8] of — 0.0010  0.0006 Example 8 D) 2-Methyl-4-phenyl-2-butanol 0.08 — —Perfume oil P1 according to 0.20 0.40 0.25 Example 14 Perfume oil P2according to — — 0.15 Example 14 Water Ad 100 Ad 100 Ad 100

Example 19 Clear Shampoo Compositions with UV-Protection

A B C Ingredient in wt. % in wt. % in wt. % Polyquaternium-7 0.50 0.500.65 Disodium Phenyl Dibenzimidazole 0.50 — — Tetrasulfonate ButylMethoxydibenzoylmethane (Avobenzone) 0.25 — 0.80 PhenylbenzimidazoleSulfonic Acid, Sodium 0.80 1.00 1.20 Salt Amino Methyl Propanol 0.500.60 0.40 Sodium Laureth Sulfate (SLES), 28% in water 30.00  25.00 20.00  Cocoamidopropyl Betaine 5.00 6.00 7.50 Propylene Glycol, PEG-55Propylene Glycol 0.80 0.80 0.80 Dioleate Panthenol 1.00 0.40 — Allantoin— 0.25 0.50 Methylparaben, Ethylparaben, — 0.30 0.55 Butylparaben,Propylparaben, Isopropylparaben, Isobutylparaben, BenzylparabenPhenoxyethanol — 0.25 — 1,2-Propylene Glycol 1.00 — 0.30 Glycerin — 1.000.60 Sodium Chloride 0.70 0.60 0.70 Extract [X7] of  0.0025 —  0.0004Example 8 B-1) Extract [X8] of —  0.0010  0.0005 Example 8 D) Perfumeoil P1 according to 0.40 0.35 0.25 Example 14 Perfume oil P2 accordingto — 0.10 0.15 Example 14 Water Ad 100 Ad 100 Ad 100

Example 20 Wetting Compositions for Wet Wipes

A B C D Ingredient in wt. % in wt. % in wt. % in wt. % Ceteraylisononanoate, Ceterareth-20, Stearyl 3.00 — — 2.50 alcohol, Glycerylstearate, Glycerin, Ceterareth-21, Cetyl palmitate Mineral oil 3.00 —3.00 — Paraffinum liquidum — — 4.00 — Ethylhexyl ethylhexanoate — — 5.00— Cetearyl ethylhexanoate — — 3.50 — PEG-40 Hydrogenated castor oil,Trideceth-9, — 2.00 — — Propylene glycol, water Citric acid, anhydrous —0.01 — — Vitamin E Acetate (Tocopheryl Acetate) 0.10 — — 0.08Phenoxyethanol 0.40 — — 0.10 Imidazolinyl urea — 0.10 — — Diazolidinylurea — — 0.15 0.05 Benzethonium chloride — 0.05 — 0.05(−)-Alpha-Bisabolol, natural — — 0.09 0.10 Chamomile extract — 0.35 — —Allantoin 0.10 — 0.08 — Acrylates/C10-30 Acrylates Copolymer — — 0.20 —Glycerin 0.50 — — — 1,2-Pentandiol 2.00 — — 0.50 1,2-Hexandiol 1.00 — —1.50 1,2-Propylene glycol — 8.00 — 2.00 Extract [X7] of  0.0012 — 0.0004  0.0001 Example 8 B-1) Extract [X8] of —  0.0010  0.0004  0.0003Example 8 D) Lavender oil — — — 0.05 Perfume oil P1 according to — 0.100.25 — Example 14 Perfume oil P2 according to — 0.01 — — Example 14Water Ad 100 Ad 100 Ad 100 Ad 100 The emulsions/lotions A, C and D wereeach applied separately to a nonwoven fabric to produce wet wipes(premoistened wipes). Solution B was applied to woven fabric sheets.

Example 21 Wetting Compositions for Wet Wipes

A B C D Ingredient in wt. % in wt. % in wt. % in wt. % Sodium chloride1.25 2.10 2.60 1.50 Zinc chloride 0.50 0.50 — 0.25 Glycerin 1.00 1.300.50 1.50 1,2-Butylene glycol — 0.40 0.80 — DMDM Hydantoin — 0.10 — 0.10Phenoxyethanol — — 0.40 — Imidazolinyl urea 0.10 — — 0.05 Cyclodextrins— 0.15 — 0.20 Acyl Glutamate 1.00 — 0.90 1.10 (surfactant) Dimethiconoland TEA 0.70 0.50 0.60 0.80 Dodecylbenzene sulfonate PEG-75 Lanolin 0.250.75 0.50 0.60 Polysorbate 20 0.22 0.40 0.30 0.50 Malic acid 0.05 0.070.10 0.10 Extract [X7] of  0.0008 —  0.0002  0.0003 Example 8 B-1)Extract [X8] of —  0.0006  0.0002  0.0004 Example 8 D) Chamomile extract— — — 0.10 Rose and lavender — — — 0.05 perfume oil Perfume oil P1 0.080.15 — — according to Example 14 Water Ad 100 Ad 100 Ad 100 Ad 100 Thecompositions A-D were each applied separately to a nonwoven fabric toproduce wet wipes.

Example 22 Cosmetic O/W—Lotions

A B C D Ingredient in wt. % in wt. % in wt. % in wt. % Paraffin oil 5.005.00 5.00 5.00 Isopropyl palmitate 5.00 5.00 5.00 5.00 Cetyl alcohol2.00 — 1.00 2.00 Stearyl alcohol — 2.00 1.00 — Beeswax 2.00 2.00 1.002.00 Ceteareth-20 2.00 2.00 2.00 2.00 PEG-20-glyceryl stearate 1.50 1.501.50 1.50 Glycerine 3.00 3.00 4.00 2.00 1,2-Butylene glycol/ — 0.50 —1.50 1,2-Propylene glycol (1:1) Phenoxyethanol — 0.25 — 0.15 Extract[X7] of  0.001 —  0.0004  0.0007 Example 8 B-1) Extract [X8] of — 0.0005  0.0006 — Example 8 D) Perfume oil P1 according 0.75 0.10 0.45 —to Example 14 Perfume oil P2 according — 0.40 0.25 0.70 to Example 14Water Ad 100 Ad 100 Ad 100 Ad 100

Example 23 Cosmetic O/W Sunprotection Compositions

A B C Ingredient in wt. % in wt. % in wt. % Glyceryl Oleate Citrate,Caprylic/Capric Triglyceride 2.00 — 2.00 Potassium Cetyl Phosphate —1.50 — Cetearyl alcohol — 1.00 — C12-15 - Alkyl Benzoate — 2.50 —Homosalate 5.00 2.00 5.00 Butyl Methoxydibenzoylmethane (Avobenzone)3.00 3.00 3.00 Ethylhexyl Salicylate 3.00 4.00 3.00 Octocrylene — 5.50 —Isoamyl p-Methoxycinnamate — 3.00 — Diisopropyl Adipate 6.00 — 6.00Ethylhexyl Isononanoate — 2.00 — Diethylhexyl 2,6 Naphthalate 1.50 —2.00 Disodium EDTA 0.10 0.10 0.10 Vitamin E Acetate (Tocopheryl Acetate)0.50 0.50 0.50 Micronized rutile (TiO₂), Alumina (9.5%) and — 3.00 0.80Simethicone (2%) Dimethicone 1.00 2.00 1.30 (−)-Alpha-Bisabolol, natural0.10 0.10 0.15 Allantoin 0.10 — 0.15 Acrylates/C10-30 AcrylatesCopolymer 0.25 — 0.25 Carbomer — 0.20 — Xanthan Gum — 0.20 — SodiumCetearyl Sulfate — 0.60 — Phenylbenzimidazole Sulfonic Acid, SodiumSalt, 35% 2.50 3.00 2.00 solution in water, neutralized withtriethanolamine Disodium Phenyl Dibenzimidazole Tetrasulfonate, 30% —2.00 — solution in water, neutralized with triethanolamineTris-Hydroxyaminomethane 0.45 — 0.50 Glycerin 4.00 1.00 3.001,2-Butylene glycol and 1,3-Butylene glycol (1:1) 3.00 — 2.00 Extract[X7] of  0.0016 —  0.0004 Example 8 B-1) Extract [X8] of —  0.0004 0.0004 Example 8 D) Perfume oil P1 according to Example 14 0.25 0.200.15 Perfume oil P2 according to Example 14 — 0.10 0.25 Water Ad 100 Ad100 Ad 100 Compositions A and C are sunsprays, composition B is asunscreen softcream.

Compositions A and C are sunsprays, composition B is a sunscreensoftcream.

Example 24 Hand Sanitizing Composition

A clear liquid composition having a pH-value of 5.6 was preparedconsisting of 2-propanol (45 wt. %), 1-propanol (30 wt. %), lactic acid(0.3 wt. %), 1-tetradecanol, medium chain triglycerides, glycerol,sodium lactate, extract [X7] of Example 8B-1) (25 ppm), and water.

Example 25 Hand Sanitizing Composition

A clear liquid composition having a pH-value of 5.3 was preparedconsisting of 1-propanol (40 wt. %), 2-propanol (28 wt. %), citric acid(0.2 wt. %), lactic acid (0.15 wt. %), 1-dodecanol, medium chaintriglycerides, glycerol, 1,2-propylene glycol, extract [X8] of Example8D) (45 ppm), and water.

Example 26 Hand Sanitizing Composition

A composition was prepared consisting of ethanol (55 wt. %), 1-propanol(10 wt. %), 1,2-propylene glycol (6 wt. %), 1,3-butylene glycol, lacticacid, extract [X8] of Example 8D) (15 ppm), and water.

Example 27 Medical Sanitizing/Disinfecting Compositions

A B C D Ingredient in wt. % in wt. % in wt. % in wt. % Benzalkoniumchloride 2.00 2.50 0.10 0.15 Cocopropylenediamine guanidinium acetate14.00  14.00  0.25 — Phenoxypropanol 35.00  30.00  0.50 —Tetrakis-(2-hydroxypropyl)-N,N,N′,N′- 5.00 — 0.08 — ethylenediamineDisodium EDTA — 1.00 0.10 0.05 Laurylpropylenediamine — 4.50 — 0.10Maleic acid 0.45 0.15 0.02 0.01 Citric acid — 0.25 — 0.01 Tridecylethoxylate-12EO 15.00  — 0.15 0.05 Tridecyl ethoxylate-5EO — 10.00  0.100.20 Ethanol 8.00 10.00  0.25 0.20 1-Propanol 1.00 — — 0.10 Extract [X7]of 0.10 —  0.0004  0.0007 Example 8 B-1) Extract [X8] of — 0.08  0.0006— Example 8 D) Perfume oil P1 according to 1.55 0.90 0.05 — Example 14Perfume oil P2 according to — 0.40 — — Example 14 Water Ad 100 Ad 100 Ad100 Ad 100 Compositions A and B are concentrates which are diluted withwater in a ratio (concentrate:water) in the range of 1:80 to 1:20 togive a ready-to-use solution. Compositions C and D are ready-to-usesolutions.

Example 28 Ready-to-Use Sanitizing/Disinfecting Compositions

A B C D Ingredient in wt. % in wt. % in wt. % in wt. % Benzalkoniumchloride 0.20 0.05 — — Ethylhexylglycerin (Octoxyglycerin) 0.25 0.200.25 — Octenidine dihydrochloride — 0.07 — 0.10 Laureth-35 0.02 — 0.01 —Sodium gluconate — 0.40 — 0.30 Glycerol 2.10 2.50 1.50 3.00Mecetroniumetilsulfate — — 0.15 — Phenoxypropanol — — — 1.00Cocoamidopropyl betaine — 0.30 0.25 — 2-Propanol 0.50 — — 0.45 Extract[X7] of  0.002 —  0.0006  0.0007 Example 8 B-1) Extract [X8] of —  0.001 0.0003 — Example 8 D) Lemon perfume oil — 0.10 0.05 — Water Ad 100 Ad100 Ad 100 Ad 100

1. Method of preservating a material or imparting antimicrobialproperties to said material, said method comprising adding to saidmaterial an effective amount therefor of a compound of the formula I, ora mixture of two or more such compounds of the formula I,

wherein m is 3 to 5, n is 2 to 5, o is 0 or 1 and p is 3 to 17, with theproviso that the sum m+n+o+p is not less than 14; and R is acarbohydrate moiety bound via one of its carbon atoms to the bindingoxygen, and/or a physiologically, especially pharmaceutically ornutraceutically or cosmetically, acceptable salt thereof, or an esterthereof, where the compound may be present in open chain form and/or inthe form of a lactone, where said material is selected from the groupconsisting of a cosmetic, a food, a beverage, a pharmaceutical, amedical device, and an active packaging material.
 2. Method according toclaim 1, where the material to which the compound is added is acosmetic, a food or a beverage.
 3. Method according to claim 1, where inthe compound of the formula I m is 3 to 5, n is 2 to 5, o is 0 or 1, pis 5 to 15 and R is a moiety of the subformula

wherein the rings A, B and C are monosaccharide moieties eachindependently from the others with 5 or 6 ring members, wherein one ormore of the hydroxyl groups may be acylated.
 4. Method according toclaim 1, wherein the compound or mixture of compounds of the formula Icomprises at least one compound selected from the group of compoundswith the following formulae:

or a physiologically acceptable salt thereof.
 5. Method according toclaim 1, where at least one additional preservative is added.
 6. Methodaccording to claim 1, where the compound or compounds of the formula I,a physiologically acceptable salt thereof, and/or an ester thereof, isadded in the form of an extract from a natural source or obtained fromsuch an extract.
 7. Method according to claim 6, where the source of theextract is Dacryopinax spathularia strain FU50088, Ditiola radicatastrain MUCL 53180, Ditiola nuda strain CBS 173.60 or Femsjonialuteo-alba (=Ditiola pezizaeformis) strain MUCL
 53500. 8. A compound ora mixture of compounds of the formula I:

wherein m is 3 to 5, n is 2 to 5, o is 0 or 1 and p is 3 to 17, with theproviso that the sum m+n+o+p is not less than 14; and R is acarbohydrate moiety bound via one of its carbon atoms to the bindingoxygen, and/or a physiologically, especially pharmaceutically ornutraceutically or cosmetically, acceptable salt thereof, or an esterthereof, where the moiety R carries at least one hydroxyl groupesterified with an acid with 3 or more carbon atoms, where the compoundmay be present in open chain form and/or in the form of a lactone, or aphysiologically acceptable salt, and/or an ester thereof.
 9. A compoundof the formula I according to claim 8, which is selected from the groupconsisting of compounds represented in the following table:

and physiologically acceptable salts and esters thereof.
 10. Apreservative or antimicrobial composition, comprising as active agent acompound or a mixture of compounds of the formula I, a physiologicallyacceptable salt thereof, and/or an ester thereof, as shown or defined inclaim 8, alone or with another additive, optionally a carrier material.11. The composition according to claim 10, which is a precursor of abeverage.
 12. An extract comprising one or more compounds of the formulaI, a physiologically acceptable salt thereof, and/or an ester thereof,as shown or defined in claim
 8. 13. A method of enhancing microbialstability of a material, comprising adding one or more compounds of theformula I, a physiologically acceptable salt thereof, and/or an esterthereof, as shown or defined in claim 8 to a material, selected from thegroup consisting of a cosmetic, a food, a beverage, a pharmaceutical, amedical device, and an active packaging material.
 14. A materialcomprising, as or within a coating and/or as admixture, an additive inthe form of a compound or a mixture of compounds of the formula I, aphysiologically acceptable salt thereof and/or an ester thereof, asdefined in claim 8, which material is a cosmetic, a food, a beverage, apharmaceutical, a medical device, or an active packaging material. 15.The material according to claim 14, where the beverage is selected fromthe group consisting of water, flavoured water, fortified water, aflavoured beverage, carbonated water, a juice, cola, lemon-lime, gingerale, root beer beverages which are carbonated in the manner of softdrinks, a syrup, a diet beverages, a carbonated soft drink, a fruitjuice, other fruit containing beverages which provide the flavor offruit juices and contain greater than 0% fruit juice but less than 100%fruit juice, fruit flavored beverages, vegetable juices, vegetablecontaining beverages, which provide the flavor of any of theaforementioned vegetable juices and contain greater than 0% vegetablejuice but less than 100% vegetable juice, isotonic beverages,non-isotonic beverages, soft drinks containing a fruit juice, coffee,tea, tea beverages prepared from tea concentrate, extracts, or powders,drinkable dairy products, hot chocolate, chocolate powders/mixes,drinkable soy products, non-diary milks, alcoholic beverages, fruitsmoothies, horchata, sport drinks, energy drinks, health drinks,wellness drinks, shakes, protein drinks, drinkable soy yogurts, low acidbeverages, acidified beverages, nectars, tonics, frozen carbonatedbeverages, frozen uncarbonated beverages, liquid meal replacements,infant formulations, and combinations or mixtures thereof; or thematerial is a cosmetic selected from a cream, emulsion, lotion, gel oroil for the skin; a face masks, a tinted base, a make-up powder, anafter-bath powder, a hygienic powder, a toilet soap, a deodorant soap, aperfumes, a toilet water, an eau de Cologne, a bath or showerpreparation; a depilatory; a deodorant, an anti-perspirant, a hair careproduct; a setting product; a cleansing product; a conditioning product;a hairdressing product; a shaving products; a product for making up andremoving make-up from the face and the eyes, a product intended forapplication to the lips, a products for care of the teeth and/or themouth; a product for nail care and/or make-up, a product for externalintimate hygiene, a sunbathing product, a product for tanning withoutsun, a skin-whitening product, an anti-wrinkle product, a tampon, asanitary towel, a diaper and a handkerchief.
 16. A material obtained bythe method according to claim 1.